Publications

multiple mutations and increased rna expression in tetracycline-resistant streptococcus pneumoniae as determined by genome-wide dna and mrna sequencing.	the objective of this study was to characterize chromosomal mutations associated with resistance to tetracycline in streptococcus pneumoniae.	2015	25862682
parallel structural evolution of mitochondrial ribosomes and oxphos complexes.	the five macromolecular complexes that jointly mediate oxidative phosphorylation (oxphos) in mitochondria consist of many more subunits than those of bacteria, yet, it remains unclear by which evolutionary mechanism(s) these novel subunits were recruited. even less well understood is the structural evolution of mitochondrial ribosomes (mitoribosomes): while it was long thought that their exceptionally high protein content would physically compensate for their uniquely low amount of ribosomal rna ...	2015	25861818
molecular determinants of the interactions between proteins and ssdna.	ssdna binding proteins (ssbs) protect ssdna from chemical and enzymatic assault that can derail dna processing machinery. complexes between ssbs and ssdna are often highly stable, but predicting their structures is challenging, mostly because of the inherent flexibility of ssdna and the geometric and energetic complexity of the interfaces that it forms. here, we report a newly developed coarse-grained model to predict the structure of ssb-ssdna complexes. the model is successfully applied to pre ...	2015	25855635
identification of novel esterase-active enzymes from hot environments by use of the host bacterium thermus thermophilus.	functional metagenomic screening strategies, which are independent of known sequence information, can lead to the identification of truly novel genes and enzymes. since e. coli has been used exhaustively for this purpose as a host, it is important to establish alternative expression hosts and to use them for functional metagenomic screening for new enzymes. in this study we show that thermus thermophilus hb27 is an excellent screening host and can be used as an alternative provider of truly nove ...	2015	25904908
two duplicated genes ddi2 and ddi3 in budding yeast encode a cyanamide hydratase and are induced by cyanamide.	two dna damage-inducible genes in saccharomyces cerevisiae, ddi2 and ddi3, are identical and encode putative hd domain-containing proteins, whose functions are currently unknown. because ddi2/3 also shows limited homology to a fungal cyanamide hydratase that converts cyanamide to urea, we tested the enzymatic activity of recombinant ddi2. to this end, we developed a novel enzymatic assay and determined that the km value of the recombinant ddi2/3 for cyanamide is 17.3 ± 0.05 mm, and its activity ...	2015	25847245
productive mrna stem loop-mediated transcriptional slippage: crucial features in common with intrinsic terminators.	escherichia coli and yeast dna-dependent rna polymerases are shown to mediate efficient nascent transcript stem loop formation-dependent rna-dna hybrid realignment. the realignment was discovered on the heteropolymeric sequence t5c5 and yields transcripts lacking a c residue within a corresponding u5c4. the sequence studied is derived from a roseiflexus insertion sequence (is) element where the resulting transcriptional slippage is required for transposase synthesis. the stability of the rna str ...	2015	25848054
ribosome biochemistry in crystal structure determination.		2015	25780230
rrna--the evolution of that magic molecule.		2015	25780167
reflections on the 20th anniversary of rna.		2015	25780133
the vrra srna controls a stationary phase survival factor vrp of vibrio cholerae.	small non-coding rnas (srnas) are emerging regulatory elements in bacteria. the vibrio cholerae srna vrra has previously been shown to down-regulate outer membrane proteins (ompa and ompt) and biofilm matrix protein (rbmc) by base-pairing with the 5' region of the corresponding mrnas. in this study, we present an additional target of vrra in v. cholerae, the mrna coding for the ribosome binding protein vrp. vrp is homologous to ribosome-associated inhibitor a (raia) of escherichia coli which fac ...	2015	25826569
identification of a laccase glac15 from ganoderma lucidum 77002 and its application in bioethanol production.	laccases have potential applications in detoxification of lignocellulosic biomass after thermochemical pretreatment and production of value-added products or biofuels from renewable biomass. however, their application in large-scale industrial and environmental processes has been severely thwarted by the high cost of commercial laccases. therefore, it is necessary to identify new laccases with lower cost but higher activity to detoxify lignocellulosic hydrolysates and better efficiency to produc ...	2015	25883681
triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate.	the widespread emergence of plasmodium falciparum (pf) strains resistant to frontline agents has fuelled the search for fast-acting agents with novel mechanism of action. here, we report the discovery and optimization of novel antimalarial compounds, the triaminopyrimidines (taps), which emerged from a phenotypic screen against the blood stages of pf. the clinical candidate (compound 12) is efficacious in a mouse model of pf malaria with an ed99 <30 mg kg(-1) and displays good in vivo safety mar ...	2015	25823686
interaction of trna with eukaryotic ribosome.	this paper is a review of currently available data concerning interactions of trnas with the eukaryotic ribosome at various stages of translation. these data include the results obtained by means of cryo-electron microscopy and x-ray crystallography applied to various model ribosomal complexes, site-directed cross-linking with the use of trna derivatives bearing chemically or photochemically reactive groups in the cca-terminal fragment and chemical probing of 28s rrna in the region of the peptid ...	2015	25830484
how fast-growing bacteria robustly tune their ribosome concentration to approximate growth-rate maximization.	maximization of growth rate is an important fitness strategy for bacteria. bacteria can achieve this by expressing proteins at optimal concentrations, such that resources are not wasted. this is exemplified for escherichia coli by the increase of its ribosomal protein-fraction with growth rate, which precisely matches the increased protein synthesis demand. these findings and others have led to the hypothesis that e. coli aims to maximize its growth rate in environments that support growth. howe ...	2015	25754869
crystal structure of the c-terminal 2',5'-phosphodiesterase domain of group a rotavirus protein vp3.	in response to viral infections, the mammalian innate immune system induces the production of the second messenger 2'-5' oligoadenylate (2-5a) to activate latent ribonuclease l (rnase l) that restricts viral replication and promotes apoptosis. a subset of rotaviruses and coronaviruses encode 2',5'-phosphodiesterase enzymes that hydrolyze 2-5a, thereby inhibiting rnase l activation. we report the crystal structure of the 2',5'-phosphodiesterase domain of group a rotavirus protein vp3 at 1.39 å re ...	2015	25758703
the conserved endoribonuclease ybey is required for chloroplast ribosomal rna processing in arabidopsis.	maturation of chloroplast ribosomal rnas (rrnas) comprises several endoribonucleolytic and exoribonucleolytic processing steps. however, little is known about the specific enzymes involved and the cleavage steps they catalyze. here, we report the functional characterization of the single arabidopsis (arabidopsis thaliana) gene encoding a putative ybey endoribonuclease. atybey null mutants are seedling lethal, indicating that atybey function is essential for plant growth. knockdown plants display ...	2015	25810095
autonomously folding protein fragments reveal differences in the energy landscapes of homologous rnases h.	an important approach to understanding how a protein sequence encodes its energy landscape is to compare proteins with different sequences that fold to the same general native structure. in this work, we compare e. coli and t. thermophilus homologs of the protein rnase h. using protein fragments, we create equilibrium mimics of two different potential partially-folded intermediates (i(core) and i(core+1)) hypothesized to be present on the energy landscapes of these two proteins. we observe that ...	2015	25803034
glycosylation of phenolic compounds by the site-mutated β-galactosidase from lactobacillus bulgaricus l3.	β-galactosidases can transfer the galactosyl from lactose or galactoside donors to various acceptors and thus are especially useful for the synthesis of important glycosides. however, these enzymes have limitations in the glycosylation of phenolic compounds that have many physiological functions. in this work, the β-galactosidase from lactobacillus bulgaricus l3 was subjected to site-saturation mutagenesis at the w980 residue. the recombinant pet-21b plasmid carrying the enzyme gene was used as ...	2015	25803778
x-ray crystal structures of escherichia coli rna polymerase with switch region binding inhibitors enable rational design of squaramides with an improved fraction unbound to human plasma protein.	squaramides constitute a novel class of rna polymerase inhibitors of which genetic evidence and computational modeling previously have suggested an inhibitory mechanism mediated by binding to the rna polymerase switch region. an iterative chemistry program increased the fraction unbound to human plasma protein from below minimum detection levels, i.e., <1% to 4-6%, while retaining biochemical potency. since in vitro antimicrobial activity against an efflux-negative strain of haemophilus influenz ...	2015	25798859
a universal stress protein (usp) in mycobacteria binds camp.	mycobacteria are endowed with rich and diverse machinery for the synthesis, utilization, and degradation of camp. the actions of cyclic nucleotides are generally mediated by binding of camp to conserved and well characterized cyclic nucleotide binding domains or structurally distinct cgmp-specific and -regulated cyclic nucleotide phosphodiesterase, adenylyl cyclase, and e. coli transcription factor fhla (gaf) domain-containing proteins. proteins with cyclic nucleotide binding and gaf domains can ...	2015	25802331
inducible expression of a resistance-nodulation-division-type efflux pump in staphylococcus aureus provides resistance to linoleic and arachidonic acids.	although staphylococcus aureus is exposed to antimicrobial fatty acids on the skin, in nasal secretions, and in abscesses, a specific mechanism of inducible resistance to this important facet of innate immunity has not been identified. here, we have sequenced the genome of s. aureus usa300 variants selected for their ability to grow at an elevated concentration of linoleic acid. the fatty acid-resistant clone far7 had a single nucleotide polymorphism resulting in an h₁₂₁y substitution in an unch ...	2015	25802299
a functional role of rv1738 in mycobacterium tuberculosis persistence suggested by racemic protein crystallography.	protein 3d structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. rv1738, a protein from mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. chemical synthesis of the l- and d-enantiomeric forms of rv1738 enabled facile crystallization of the d/l-racemic mixture. the structure was solved by an ab initio ap ...	2015	25831534
structural and functional studies of phosphoenolpyruvate carboxykinase from mycobacterium tuberculosis.	tuberculosis, the second leading infectious disease killer after hiv, remains a top public health priority. the causative agent of tuberculosis, mycobacterium tuberculosis (mtb), which can cause both acute and clinically latent infections, reprograms metabolism in response to the host niche. phosphoenolpyruvate carboxykinase (pck) is the enzyme at the center of the phosphoenolpyruvate-pyruvate-oxaloacetate node, which is involved in regulating the carbon flow distribution to catabolism, anabolis ...	2015	25798914
ph dependence of the stress regulator dksa.	dksa controls transcription of genes associated with diverse stress responses, such as amino acid and carbon starvation, oxidative stress, and iron starvation. dksa binds within the secondary channel of rna polymerase, extending its long coiled-coil domain towards the active site. the cellular expression of dksa remains constant due to a negative feedback autoregulation, raising the question of whether dksa activity is directly modulated during stress. here, we show that escherichia coli dksa is ...	2015	25799498
the phenotypic expression of mitochondrial trna-mutations can be modulated by either mitochondrial leucyl-trna synthetase or the c-terminal domain thereof.	mutations in mitochondrial (mt) dna determine important human diseases. the majority of the known pathogenic mutations are located in transfer rna (trna) genes and are responsible for a wide range of currently untreatable disorders. experimental evidence both in yeast and in human cells has shown that the detrimental effects of mt-trna point mutations can be attenuated by increasing the expression of the cognate mt-aminoacyl-trna synthetases (aarss). in addition, constitutive high levels of isol ...	2015	25852750
unraveling the specific regulation of the central pathway for anaerobic degradation of 3-methylbenzoate.	the mbd cluster encodes the anaerobic degradation of 3-methylbenzoate in the β-proteobacterium azoarcus sp. cib. the specific transcriptional regulation circuit that controls the expression of the mbd genes was investigated. the po, pb 1, and p3 r promoters responsible for the expression of the mbd genes, their cognate mbdr transcriptional repressor, as well as the mbdr operator regions (atacn10gtat) have been characterized. the three-dimensional structure of mbdr has been solved revealing a con ...	2015	25795774
overexpression of a novel thermostable and chloride-tolerant laccase from thermus thermophilus sg0.5jp17-16 in pichia pastoris and its application in synthetic dye decolorization.	laccases have been used for the decolorization and detoxification of synthetic dyes due to their ability to oxidize a wide variety of dyes with water as the sole byproduct. a putative laccase gene (lactt) from thermus thermophilus sg0.5jp17-16 was screened using the genome mining approach, and it was highly expressed in pichia pastoris, yielding a high laccase activity of 6130 u/l in a 10-l fermentor. the lactt open reading frame encoded a protein of 466 amino acid residues with four putative cu ...	2015	25790466
high-resolution structure of the escherichia coli ribosome.	protein synthesis by the ribosome is highly dependent on the ionic conditions in the cellular environment, but the roles of ribosome solvation have remained poorly understood. moreover, the functions of modifications to ribosomal rna and ribosomal proteins have also been unclear. here we present the structure of the escherichia coli 70s ribosome at 2.4-å resolution. the structure reveals details of the ribosomal subunit interface that are conserved in all domains of life, and it suggests how sol ...	2015	25775265
structural insights into the role of rrna modifications in protein synthesis and ribosome assembly.	we report crystal structures of the thermus thermophilus ribosome at 2.3- to 2.5-å resolution, which have enabled modeling of rrna modifications. the structures reveal contacts of modified nucleotides with mrna and trnas or protein py, and contacts within the ribosome interior stabilizing the functional fold of rrna. our work provides a resource to explore the roles of rrna modifications and yields a more comprehensive atomic model of a bacterial ribosome.	2015	25775268
universal pathway for posttransfer editing reactions: insights from the crystal structure of ttphers with puromycin.	at the amino acid binding and recognition step, phenylalanyl-trna synthetase (phers) faces the challenge of discrimination between cognate phenylalanine and closely similar noncognate tyrosine. resampling of tyr-trna(phe) to phers increasing the number of correctly charged trna molecules has recently been revealed. thus, the very same editing site of phers promotes hydrolysis of misacylated trna species, associated both with cis- and trans-editing pathways. here we report the crystal structure o ...	2015	25775602
substrate, product, and cofactor: the extraordinarily flexible relationship between the cde superfamily and heme.	pfam clan 0032, also known as the cde superfamily, is a diverse group of at least 20 protein families sharing a common α,β-barrel domain. of these, six different groups bind heme inside the barrel's interior, using it alternately as a cofactor, substrate, or product. focusing on these six, an integrated picture of structure, sequence, taxonomy, and mechanism is presented here, detailing how a single structural motif might be able to mediate such an array of functions with one of nature's most im ...	2015	25778630
the ingenious structure of central rotor apparatus in vov1; key for both complex disassembly and energy coupling between v1 and vo.	vacuolar type rotary h+-atpases (vov1) couple atp synthesis/hydrolysis by v1 with proton translocation by vo via rotation of a central rotor apparatus composed of the v1-df rotor shaft, a socket-like vo-c (eukaryotic vo-d) and the hydrophobic rotor ring. reconstitution experiments using subcomplexes revealed a weak binding affinity of v1-df to vo-c despite the fact that torque needs to be transmitted between v1-df and vo-c for the tight energy coupling between v1 and vo. mutation of a short heli ...	2015	25756791
a prime/boost strategy using dna/fowlpox recombinants expressing the genetically attenuated e6 protein as a putative vaccine against hpv-16-associated cancers.	considering the high number of new cases of cervical cancer each year that are caused by human papilloma viruses (hpvs), the development of an effective vaccine for prevention and therapy of hpv-associated cancers, and in particular against the high-risk hpv-16 genotype, remains a priority. vaccines expressing the e6 and e7 proteins that are detectable in all hpv-positive pre-cancerous and cancer cells might support the treatment of hpv-related lesions and clear already established tumors.	2015	25763880
phylogenetic analysis of vitamin b12-related metabolism in mycobacterium tuberculosis.	comparison of genome sequences from clinical isolates of mycobacterium tuberculosis with phylogenetically-related pathogens mycobacterium marinum, mycobacterium kansasii, and mycobacterium leprae reveals diversity amongst genes associated with vitamin b12-related metabolism. diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (snps) with predicted impact on protein function and transcriptional regulation. d ...	2015	25988174
evolution of the metazoan mitochondrial replicase.	the large number of complete mitochondrial dna (mtdna) sequences available for metazoan species makes it a good system for studying genome diversity, although little is known about the mechanisms that promote and/or are correlated with the evolution of this organellar genome. by investigating the molecular evolutionary history of the catalytic and accessory subunits of the mtdna polymerase, pol γ, we sought to develop mechanistic insight into its function that might impact genome structure by ex ...	2015	25740821
structure of the vacuolar h+-atpase rotary motor reveals new mechanistic insights.	vacuolar h(+)-atpases are multisubunit complexes that operate with rotary mechanics and are essential for membrane proton transport throughout eukaryotes. here we report a ∼ 1 nm resolution reconstruction of a v-atpase in a different conformational state from that previously reported for a lower-resolution yeast model. the stator network of the v-atpase (and by implication that of other rotary atpases) does not change conformation in different catalytic states, and hence must be relatively rigid ...	2015	25661654
supramolecular protein assembly supports immobilization of a cytochrome p450 monooxygenase system as water-insoluble gel.	diverse applications of the versatile bacterial cytochrome p450 enzymes (p450s) are hampered by their requirement for the auxiliary proteins, ferredoxin reductases and ferredoxins, that transfer electrons to p450s. notably, this limits the use of p450s as immobilized enzymes for industrial purposes. herein, we demonstrate the immobilization of a bacterial p450 and its redox protein partners by supramolecular complex formation using a self-assembled heterotrimeric protein. employment of homodimer ...	2015	25733255
heterotrimeric nadh-oxidizing methylenetetrahydrofolate reductase from the acetogenic bacterium acetobacterium woodii.	the methylenetetrahydrofolate reductase (mthfr) of acetogenic bacteria catalyzes the reduction of methylene-thf, which is highly exergonic with nadh as the reductant. therefore, the enzyme was suggested to be involved in energy conservation by reducing ferredoxin via electron bifurcation, followed by na(+) translocation by the rnf complex. the enzyme was purified from acetobacterium woodii and shown to have an unprecedented subunit composition containing the three subunits rnfc2, metf, and metv. ...	2015	25733614
role of nad⁺-dependent malate dehydrogenase in the metabolism of methylomicrobium alcaliphilum 20z and methylosinus trichosporium ob3b.	we have expressed the l-malate dehydrogenase (mdh) genes from aerobic methanotrophs methylomicrobium alcaliphilum 20z and methylosinus trichosporium ob3b as his-tagged proteins in escherichia coli. the substrate specificities, enzymatic kinetics and oligomeric states of the mdhs have been characterized. both mdhs were nad⁺-specific and thermostable enzymes not affected by metal ions or various organic metabolites. the mdh from m. alcaliphilum 20z was a homodimeric (2 × 35 kda) enzyme displaying ...	2015	27682078
trna biology in mitochondria.	mitochondria are the powerhouses of eukaryotic cells. they are considered as semi-autonomous because they have retained genomes inherited from their prokaryotic ancestor and host fully functional gene expression machineries. these organelles have attracted considerable attention because they combine bacterial-like traits with novel features that evolved in the host cell. among them, mitochondria use many specific pathways to obtain complete and functional sets of trnas as required for translatio ...	2015	25734984
bactobolin a binds to a site on the 70s ribosome distinct from previously seen antibiotics.	the ribosome is the target of a large number of antibiotics. here, we report a 3.4-å-resolution crystal structure of bactobolin a bound to 70s ribosome-trna complex. the antibiotic binds at a previously unseen site in the 50s subunit and displaces trna bound at the p-site. it thus likely has a similar mechanism of action as blasticidin s despite binding to a different site. the structure also rationalizes previously identified resistance mutations.	2015	25562208
unraveling the mechanistic features of rna polymerase ii termination by the 5'-3' exoribonuclease rat1.	within a complex with rai1, the 5'-3' exoribonuclease rat1 promotes termination of rna polymerase ii (rnapii) on protein-coding genes, but its underlying molecular mechanism is still poorly understood. using in vitro transcription termination assays, we have found that rnapii is prone to more effective termination by rat1/rai1 when its catalytic site is disrupted due to ntp misincorporation, implying that paused rnapii, which is often found in vivo near termination sites, could adopt a similar c ...	2015	25722373
structural basis for recognition of g-1-containing trna by histidyl-trna synthetase.	aminoacyl-trna synthetases (aarss) play a crucial role in protein translation by linking trnas with cognate amino acids. among all the trnas, only trna(his) bears a guanine base at position -1 (g-1), and it serves as a major recognition element for histidyl-trna synthetase (hisrs). despite strong interests in the histidylation mechanism, the trna recognition and aminoacylation details are not fully understood. we herein present the 2.55 å crystal structure of hisrs complexed with trna(his), whic ...	2015	25722375
an intermolecular binding mechanism involving multiple lysm domains mediates carbohydrate recognition by an endopeptidase.	lysm domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing n-acetylglucosamine (glcnac) moieties, such as chitin and peptidoglycan. in bacteria, the functional significance of the involvement of multiple lysm domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. here, a structural study of the thermus thermophilus nlpc/p60 endopeptidase cont ...	2015	25760608
identification of two structural elements important for ribosome-dependent gtpase activity of elongation factor 4 (ef4/lepa).	the bacterial translational gtpase ef4/lepa is structurally similar to the canonical elongation factor ef-g. while sharing core structural features with other translational gtpases, the function of ef4 remains unknown. recent structural data locates the unique c-terminal domain (ctd) of ef4 in proximity to the ribosomal peptidyl transferase center (ptc). to investigate the functional role of ef4's ctd we have constructed three c-terminal truncation variants. these variants are fully functional w ...	2015	25712150
analysis of the cooperative atpase cycle of the aaa+ chaperone clpb from thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.	the clpb/hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with dnak/hsp70 and its cofactors. the clpb/hsp104 protomer has two aaa+ modules, aaa-1 and aaa-2, and forms a homohexamer. in the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic aaa+ modules. by atp binding and its hydrolysis at these aaa+ modules, clpb/hsp104 exerts the mechanical power required for protein disaggregation. although atpase cycle of this chaperone has be ...	2015	25713084
hemq: an iron-coproporphyrin oxidative decarboxylase for protoheme synthesis in firmicutes and actinobacteria.	genes for chlorite dismutase-like proteins are found widely among heme-synthesizing bacteria and some archaea. it is now known that among the firmicutes and actinobacteria these proteins do not possess chlorite dismutase activity but instead are essential for heme synthesis. these proteins, named hemq, are iron-coproporphyrin (coproheme) decarboxylases that catalyze the oxidative decarboxylation of coproheme iii into protoheme ix. as purified, hemqs do not contain bound heme, but readily bind ex ...	2015	25711532
aida: ab initio domain assembly for automated multi-domain protein structure prediction and domain-domain interaction prediction.	most proteins consist of multiple domains, independent structural and evolutionary units that are often reshuffled in genomic rearrangements to form new protein architectures. template-based modeling methods can often detect homologous templates for individual domains, but templates that could be used to model the entire query protein are often not available.	2015	25701568
structure of escherichia coli dgtp triphosphohydrolase: a hexameric enzyme with dna effector molecules.	the escherichia coli dgt gene encodes a dgtp triphosphohydrolase whose detailed role still remains to be determined. deletion of dgt creates a mutator phenotype, indicating that the dgtpase has a fidelity role, possibly by affecting the cellular dntp pool. in the present study, we have investigated the structure of the dgt protein at 3.1-å resolution. one of the obtained structures revealed a protein hexamer that contained two molecules of single-stranded dna. the presence of dna caused signific ...	2015	25694425
2-thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in rna and dna duplexes.	2-thiouracil-containing nucleosides are essential modified units of natural and synthetic nucleic acids. in particular, the 5-substituted-2-thiouridines (s2us) present in trna play an important role in tuning the translation process through codon-anticodon interactions. the enhanced thermodynamic stability of s2u-containing rna duplexes and the preferred s2u-a versus s2u-g base pairing are appreciated characteristics of s2u-modified molecular probes. recently, we have demonstrated that 2-thiouri ...	2015	25690900
rna polymerase-induced remodelling of nusa produces a pause enhancement complex.	pausing during transcription elongation is a fundamental activity in all kingdoms of life. in bacteria, the essential protein nusa modulates transcriptional pausing, but its mechanism of action has remained enigmatic. by combining structural and functional studies we show that a helical rearrangement induced in nusa upon interaction with rna polymerase is the key to its modulatory function. this conformational change leads to an allosteric re-positioning of conserved basic residues that could en ...	2015	25690895
synergistic effects of atp and rna binding to human dead-box protein ddx1.	rna helicases of the dead-box protein family form the largest group of helicases. the human dead-box protein 1 (ddx1) plays an important role in trna and mrna processing, is involved in tumor progression and is also hijacked by several virus families such as hiv-1 for replication and nuclear export. although important in many cellular processes, the mechanism of ddx1's enzymatic function is unknown. we have performed equilibrium titrations and transient kinetics to determine affinities for nucle ...	2015	25690890
identification of a second gtp-bound magnesium ion in archaeal initiation factor 2.	eukaryotic and archaeal translation initiation processes involve a heterotrimeric gtpase e/aif2 crucial for accuracy of start codon selection. in eukaryotes, the gtpase activity of eif2 is assisted by a gtpase-activating protein (gap), eif5. in archaea, orthologs of eif5 are not found and aif2 gtpase activity is thought to be non-assisted. however, no in vitro gtpase activity of the archaeal factor has been reported to date. here, we show that aif2 significantly hydrolyses gtp in vitro. within a ...	2015	25690901
arginine-rhamnosylation as new strategy to activate translation elongation factor p.	ribosome stalling at polyproline stretches is common and fundamental. in bacteria, translation elongation factor p (ef-p) rescues such stalled ribosomes, but only when it is post-translationally activated. in escherichia coli, activation of ef-p is achieved by (r)-β-lysinylation and hydroxylation of a conserved lysine. here we have unveiled a markedly different modification strategy in which a conserved arginine of ef-p is rhamnosylated by a glycosyltransferase (earp) using dtdp-l-rhamnose as a ...	2015	25686373
a prokaryotic twist on argonaute function.	argonaute proteins can be found in all three domains of life. in eukaryotic organisms, argonaute is, as the functional core of the rna-silencing machinery, critically involved in the regulation of gene expression. despite the mechanistic and structural similarities between archaeal, bacterial and eukaryotic argonaute proteins, the biological function of bacterial and archaeal argonautes has remained elusive. this review discusses new findings in the field that shed light on the structure and fun ...	2015	25692904
eukaryotic lyr proteins interact with mitochondrial protein complexes.	in eukaryotic cells, mitochondria host ancient essential bioenergetic and biosynthetic pathways. lyr (leucine/tyrosine/arginine) motif proteins (lyrms) of the complex1_lyr-like superfamily interact with protein complexes of bacterial origin. many lyr proteins function as extra subunits (lyrm3 and lyrm6) or novel assembly factors (lyrm7, lyrm8, acn9 and fmc1) of the oxidative phosphorylation (oxphos) core complexes. structural insights into complex i accessory subunits lyrm6 and lyrm3 have been p ...	2015	25686363
novel flp pilus biogenesis-dependent natural transformation.	natural transformation has been described in bacterial species spread through nearly all major taxonomic groups. however, the current understanding of the structural components and the regulation of competence development is derived from only a few model organisms. although natural transformation was discovered in members of the actinobacteria (high gc gram-positive bacteria) more than four decades ago, the structural components or the regulation of the competence system have not been studied in ...	2015	25713572
the bypass of zipa by overexpression of ftsn requires a previously unknown conserved ftsn motif essential for ftsa-ftsn interaction supporting a model in which ftsa monomers recruit late cell division proteins to the z ring.	assembly of the divisome in escherichia coli occurs in two temporally distinct steps. first, ftsz filaments attached to the membrane through interaction with ftsa and zipa coalesce into a z ring at midcell. then, additional proteins are recruited to the z ring in a hierarchical manner to form a complete divisome, activated by the arrival of ftsn. recently, we proposed that the interaction of ftsa with itself competes with its ability to recruit downstream division proteins (both require the ic d ...	2015	25496259
activity of select dehydrogenases with sepharose-immobilized n(6)-carboxymethyl-nad.	n(6)-carboxymethyl-nad (n(6)-cm-nad) can be used to immobilize nad onto a substrate containing terminal primary amines. we previously immobilized n(6)-cm-nad onto sepharose beads and showed that thermotoga maritima glycerol dehydrogenase could use the immobilized cofactor with cofactor recycling. we now show that saccharomyces cerevisiae alcohol dehydrogenase, rabbit muscle l-lactate dehydrogenase (type xi), bovine liver l-glutamic dehydrogenase (type iii), leuconostoc mesenteroides glucose-6-ph ...	2015	25611453
structural basis for transcription reactivation by rapa.	rna polymerase (rnap) loses activity during transcription as it stalls at various inactive states due to erratic translocation. reactivation of these stalled rnaps is essential for efficient rna synthesis. here we report a 4.7-å resolution crystal structure of the escherichia coli rnap core enzyme in complex with atpase rapa that is involved in reactivating stalled rnaps. the structure reveals that rapa binds at the rna exit channel of the rnap and makes the channel unable to accommodate the for ...	2015	25646438
distinct pathways of rna polymerase regulation by a phage-encoded factor.	transcription antitermination is a common strategy of gene expression regulation, but only a few transcription antitermination factors have been studied in detail. here, we dissect the transcription antitermination mechanism of xanthomonas oryzae virus xp10 protein p7, which binds host rna polymerase (rnap) and regulates both transcription initiation and termination. we show that p7 suppresses intrinsic termination by decreasing rnap pausing and increasing the transcription complex stability, in ...	2015	25646468
diversity in (p)ppgpp metabolism and effectors.	bacteria produce guanosine tetraphosphate and pentaphosphate, collectively named (p)ppgpp, in response to a variety of environmental stimuli. these two remarkable molecules regulate many cellular processes, including the central dogma processes and metabolism, to ensure survival and adaptation. work in escherichia coli laid the foundation for understanding the molecular details of (p)ppgpp and its cellular functions. as recent studies expand to other species, it is apparent that there exists con ...	2015	25636134
mutations in ribosomal proteins, rpl4 and rack1, suppress the phenotype of a thermospermine-deficient mutant of arabidopsis thaliana.	thermospermine acts in negative regulation of xylem differentiation and its deficient mutant of arabidopsis thaliana, acaulis5 (acl5), shows excessive xylem formation and severe dwarfism. studies of two dominant suppressors of acl5, sac51-d and sac52-d, have revealed that sac51 and sac52 encode a transcription factor and a ribosomal protein l10 (rpl10), respectively, and these mutations enhance translation of the sac51 mrna, which contains conserved upstream open reading frames in the 5' leader. ...	2015	25625317
advancing the development of glycated protein biosensing technology: next-generation sensing molecules.	research advances in biochemical molecules have led to the development of convenient and reproducible biosensing molecules for glycated proteins, such as those based on the enzymes fructosyl amino acid oxidase (faox) or fructosyl peptide oxidase (fpox). recently, more attractive biosensing molecules with potential applications in next-generation biosensing of glycated proteins have been aggressively reported. we review 2 such molecules, fructosamine 6-kinase (fn6k) and fructosyl amino acid-bindi ...	2015	25627465
role of δ1-pyrroline-5-carboxylate dehydrogenase supports mitochondrial metabolism and host-cell invasion of trypanosoma cruzi.	proline is crucial for energizing critical events throughout the life cycle of trypanosoma cruzi, the etiological agent of chagas disease. the proline breakdown pathway consists of two oxidation steps, both of which produce reducing equivalents as follows: the conversion of proline to δ(1)-pyrroline-5-carboxylate (p5c), and the subsequent conversion of p5c to glutamate. we have identified and characterized the δ(1)-pyrroline-5-carboxylate dehydrogenase from t. cruzi (tcp5cdh) and report here on ...	2015	25623067
engineering the genome of thermus thermophilus using a counterselectable marker.	thermus thermophilus is an extremely thermophilic bacterium that is widely used as a model thermophile, in large part due to its amenability to genetic manipulation. here we describe a system for the introduction of genomic point mutations or deletions using a counterselectable marker consisting of a conditionally lethal mutant allele of phes encoding the phenylalanyl-trna synthetase α-subunit. mutant phes with an a294g amino acid substitution renders cells sensitive to the phenylalanine analog ...	2015	25605305
structural insights into mis-regulation of protein kinase a in human tumors.	the extensively studied camp-dependent protein kinase a (pka) is involved in the regulation of critical cell processes, including metabolism, gene expression, and cell proliferation; consequentially, mis-regulation of pka signaling is implicated in tumorigenesis. recent genomic studies have identified recurrent mutations in the catalytic subunit of pka in tumors associated with cushing's syndrome, a kidney disorder leading to excessive cortisol production, and also in tumors associated with fibr ...	2015	25605907
redox state of flavin adenine dinucleotide drives substrate binding and product release in escherichia coli succinate dehydrogenase.	the complex ii family of enzymes, comprising respiratory succinate dehydrogenases and fumarate reductases, catalyzes reversible interconversion of succinate and fumarate. in contrast to the covalent flavin adenine dinucleotide (fad) cofactor assembled in these enzymes, soluble fumarate reductases (e.g., those from shewanella frigidimarina) that assemble a noncovalent fad cannot catalyze succinate oxidation but retain the ability to reduce fumarate. in this study, an sdha-h45a variant that elimin ...	2015	25569225
substrate trna recognition mechanism of eubacterial trna (m1a58) methyltransferase (trmi).	trmi generates n(1)-methyladenosine at position 58 (m(1)a58) in trna. the thermus thermophilus trna(phe) transcript was methylated efficiently by t. thermophilus trmi, whereas the yeast trna(phe) transcript was poorly methylated. fourteen chimeric trna transcripts derived from these two trnas revealed that trmi recognized the combination of aminoacyl stem, variable region, and t-loop. this was confirmed by 10 deletion trna variants: trmi methylated transcripts containing the aminoacyl stem, vari ...	2015	25593312
conformational changes of elongation factor g on the ribosome during trna translocation.	the universally conserved gtpase elongation factor g (ef-g) catalyzes the translocation of trna and mrna on the ribosome after peptide bond formation. despite numerous studies suggesting that ef-g undergoes extensive conformational rearrangements during translocation, high-resolution structures exist for essentially only one conformation of ef-g in complex with the ribosome. here, we report four atomic-resolution crystal structures of ef-g bound to the ribosome programmed in the pre- and posttra ...	2015	25594181
hydrazidase, a novel amidase signature enzyme that hydrolyzes acylhydrazides.	the degradation mechanisms of natural and artificial hydrazides have been elucidated. here we screened and isolated bacteria that utilize the acylhydrazide 4-hydroxybenzoic acid 1-phenylethylidene hydrazide (hbph) from soils. physiological and phylogenetic studies identified one bacterium as microbacterium sp. strain hm58-2, from which we purified intracellular hydrazidase, cloned its gene, and prepared recombinant hydrazidase using an escherichia coli expression system. the microbacterium sp. h ...	2015	25583978
structural biology. division of labor in transhydrogenase by alternating proton translocation and hydride transfer.	nadph/nadp(+) (the reduced form of nadp(+)/nicotinamide adenine dinucleotide phosphate) homeostasis is critical for countering oxidative stress in cells. nicotinamide nucleotide transhydrogenase (th), a membrane enzyme present in both bacteria and mitochondria, couples the proton motive force to the generation of nadph. we present the 2.8 å crystal structure of the transmembrane proton channel domain of th from thermus thermophilus and the 6.9 å crystal structure of the entire enzyme (holo-th). ...	2015	25574024
identification of fah domain-containing protein 1 (fahd1) as oxaloacetate decarboxylase.	fumarylacetoacetate hydrolase (fah) domain-containing proteins occur in both prokaryotes and eukaryotes, where they carry out diverse enzymatic reactions, probably related to structural differences in their respective fah domains; however, the precise relationship between structure of the fah domain and the associated enzyme function remains elusive. in mammals, three fah domain-containing proteins, fahd1, fahd2a, and fahd2b, are known; however, their enzymatic function, if any, remains to be de ...	2015	25575590
enzyme dynamics from nmr spectroscopy.	conspectus: biological activities of enzymes, including regulation or coordination of mechanistic stages preceding or following the chemical step, may depend upon kinetic or equilibrium changes in protein conformations. exchange of more open or flexible conformational states with more closed or constrained states can influence inhibition, allosteric regulation, substrate recognition, formation of the michaelis complex, side reactions, and product release. nmr spectroscopy has long been applied t ...	2015	25574774
specific and non-specific interactions of parb with dna: implications for chromosome segregation.	the segregation of many bacterial chromosomes is dependent on the interactions of parb proteins with centromere-like dna sequences called pars that are located close to the origin of replication. in this work, we have investigated the binding of bacillus subtilis parb to dna in vitro using a variety of biochemical and biophysical techniques. we observe tight and specific binding of a parb homodimer to the pars sequence. binding of parb to non-specific dna is more complex and displays apparent po ...	2015	25572315
association between intrinsic disorder and serine/threonine phosphorylation in mycobacterium tuberculosis.	serine/threonine phosphorylation is an important mechanism that is involved in the regulation of protein function. in eukaryotes, phosphorylation occurs predominantly in intrinsically disordered regions of proteins. though serine/threonine phosphorylation and protein disorder are much less prevalent in prokaryotes, some bacteria have high levels of serine/threonine phosphorylation and disorder, including the medically important m. tuberculosis. here i show that serine/threonine phosphorylation s ...	2015	25648268
nucleoid occlusion protein noc recruits dna to the bacterial cell membrane.	to proliferate efficiently, cells must co-ordinate division with chromosome segregation. in bacillus subtilis, the nucleoid occlusion protein noc binds to specific dna sequences (nbss) scattered around the chromosome and helps to protect genomic integrity by coupling the initiation of division to the progression of chromosome replication and segregation. however, how it inhibits division has remained unclear. here, we demonstrate that noc associates with the cell membrane via an n-terminal amphi ...	2015	25568309
cdc45 (cell division cycle protein 45) guards the gate of the eukaryote replisome helicase stabilizing leading strand engagement.	dna replication licensing is now understood to be the pathway that leads to the assembly of double hexamers of minichromosome maintenance (mcm2-7) at origin sites. cell division control protein 45 (cdc45) and gins proteins activate the latent mcm2-7 helicase by inducing allosteric changes through binding, forming a cdc45/mcm2-7/gins (cmg) complex that is competent to unwind duplex dna. the cmg has an active gate between subunits mcm2 and mcm5 that opens and closes in response to nucleotide bindi ...	2015	25561522
production of dioxygen in the dark: dismutases of oxyanions.	o₂-generating reactions are exceedingly rare in biology and difficult to mimic synthetically. perchlorate-respiring bacteria enzymatically detoxify chlorite (clo₂(-) ), the end product of the perchlorate (clo(4)(-) ) respiratory pathway, by rapidly converting it to dioxygen (o₂) and chloride (cl(-)). this reaction is catalyzed by a heme-containing protein, called chlorite dismutase (cld), which bears no structural or sequence relationships with known peroxidases or other heme proteins and is par ...	2015	25707466
high throughput screen identifies natural product inhibitor of phenylalanyl-trna synthetase from pseudomonas aeruginosa and streptococcus pneumoniae.	pseudomonas aeruginosa and streptococcus pneumoniae are causative agents in a wide range of infections. genes encoding proteins corresponding to phenylalanyl-trna synthetase (phers) were cloned from both bacteria. the two forms of phers were kinetically evaluated and the k(m)'s for p. aeruginosa phers with its three substrates, phenylalanine, atp and trna(phe) were determined to be 48, 200, and 1.2 µm, respectively, while the k(m)'s for s. pneumoniae phers with respect to phenylalanine, atp and ...	2015	25601215
crystallization and preliminary x-ray analysis of the nad+-reducing [nife] hydrogenase from hydrogenophilus thermoluteolus th-1.	nad+-reducing [nife] hydrogenases catalyze the oxidoreduction of dihydrogen concomitant with the interconversion of nad+ and nadh. here, the isolation, purification and crystallization of the nad+-reducing [nife] hydrogenase from hydrogenophilus thermoluteolus th-1 are reported. crystals of the nad+-reducing [nife] hydrogenase were obtained within one week from a solution containing polyethylene glycol using the sitting-drop vapour-diffusion method and micro-seeding. the crystal diffracted to 2. ...	2015	25615977
in pursuit of an accurate spatial and temporal model of biomolecules at the atomistic level: a perspective on computer simulation.	despite huge advances in the computational techniques available for simulating biomolecules at the quantum-mechanical, atomistic and coarse-grained levels, there is still a widespread perception amongst the experimental community that these calculations are highly specialist and are not generally applicable by researchers outside the theoretical community. in this article, the successes and limitations of biomolecular simulation and the further developments that are likely in the near future are ...	2015	25615870
metagenomic analysis of hot springs in central india reveals hydrocarbon degrading thermophiles and pathways essential for survival in extreme environments.	extreme ecosystems such as hot springs are of great interest as a source of novel extremophilic species, enzymes, metabolic functions for survival and biotechnological products. india harbors hundreds of hot springs, the majority of which are not yet explored and require comprehensive studies to unravel their unknown and untapped phylogenetic and functional diversity. the aim of this study was to perform a large-scale metagenomic analysis of three major hot springs located in central india namel ...	2016	28105025
metagenomic analysis of hot springs in central india reveals hydrocarbon degrading thermophiles and pathways essential for survival in extreme environments.	extreme ecosystems such as hot springs are of great interest as a source of novel extremophilic species, enzymes, metabolic functions for survival and biotechnological products. india harbors hundreds of hot springs, the majority of which are not yet explored and require comprehensive studies to unravel their unknown and untapped phylogenetic and functional diversity. the aim of this study was to perform a large-scale metagenomic analysis of three major hot springs located in central india namel ...	2016	28105025
editorial: filamentous bacteriophage in bio/nano/technology, bacterial pathogenesis and ecology.		2016	28066406
coupled atpase-adenylate kinase activity in abc transporters.	atp-binding cassette (abc) transporters, a superfamily of integral membrane proteins, catalyse the translocation of substrates across the cellular membrane by atp hydrolysis. here we demonstrate by nucleotide turnover and binding studies based on (31)p solid-state nmr spectroscopy that the abc exporter and lipid a flippase msba can couple atp hydrolysis to an adenylate kinase activity, where adp is converted into amp and atp. single-point mutations reveal that both atpase and adenylate kinase me ...	2016	28004795
mapping the membrane proteome of anaerobic gut fungi identifies a wealth of carbohydrate binding proteins and transporters.	engineered cell factories that convert biomass into value-added compounds are emerging as a timely alternative to petroleum-based industries. although often overlooked, integral membrane proteins such as solute transporters are pivotal for engineering efficient microbial chassis. anaerobic gut fungi, adapted to degrade raw plant biomass in the intestines of herbivores, are a potential source of valuable transporters for biotechnology, yet very little is known about the membrane constituents of t ...	2016	27998268
homology-based modeling of universal stress protein from listeria innocua up-regulated under acid stress conditions.	an universal stress protein (usp) expressed under acid stress condition by listeria innocua atcc 33090 was investigated. the usp was up-regulated not only in the stationary phase but also during the exponential growth phase. the three dimensional (3d) structure of usp was predicted using a combined proteomic and bioinformatics approach. phylogenetic analysis showed that the usp from listeria detected in our study was distant from the usps of other bacteria (such as pseudomonas spp., escherichia ...	2016	28066336
comparison of lipases and glycoside hydrolases as catalysts in synthesis reactions.	lipases and glycoside hydrolases have large similarities concerning reaction mechanisms. acyl-enzyme intermediates are formed during lipase-catalyzed reactions and in an analogous way, retaining glycoside hydrolases form glycosyl-enzyme intermediates during catalysis. in both cases, the covalent enzyme intermediates can react with water or other nucleophiles containing hydroxyl groups. simple alcohols are accepted as nucleophiles by both types of enzymes. lipases are used very successfully in sy ...	2016	27995311
comparison of lipases and glycoside hydrolases as catalysts in synthesis reactions.	lipases and glycoside hydrolases have large similarities concerning reaction mechanisms. acyl-enzyme intermediates are formed during lipase-catalyzed reactions and in an analogous way, retaining glycoside hydrolases form glycosyl-enzyme intermediates during catalysis. in both cases, the covalent enzyme intermediates can react with water or other nucleophiles containing hydroxyl groups. simple alcohols are accepted as nucleophiles by both types of enzymes. lipases are used very successfully in sy ...	2016	27995311
systematic analysis of the lysine acetylome in fusarium graminearum.	lysine acetylation in proteins is a ubiquitous and conserved post-translational modification, playing a critical regulatory role in almost every aspect of living cells. although known for many years, its function remains elusive in fusarium graminearum, one of the most important necrotrophic plant pathogens with huge economic impact.	2016	27964708
the mechanism of a formaldehyde-sensing transcriptional regulator.	most organisms are exposed to the genotoxic chemical formaldehyde, either from endogenous or environmental sources. therefore, biology has evolved systems to perceive and detoxify formaldehyde. the frmra(b) operon that is present in many bacteria represents one such system. the frmr protein is a transcriptional repressor that is specifically inactivated in the presence of formaldehyde, permitting expression of the formaldehyde detoxification machinery (frma and frmb, when the latter is present). ...	2016	27934966
dynamic complexes in the chaperonin-mediated protein folding cycle.	the groel-groes chaperonin system is probably one of the most studied chaperone systems at the level of the molecular mechanism. since the first reports of a bacterial gene involved in phage morphogenesis in 1972, these proteins have stimulated intensive research for over 40 years. during this time, detailed structural and functional studies have yielded constantly evolving concepts of the chaperonin mechanism of action. despite of almost three decades of research on this oligomeric protein, cer ...	2016	28008398
structure of the 40s ribosomal subunit of plasmodium falciparum by homology and de novo modeling.	generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary structures of organisms can be generated. this is especially the case if a homologous crystal structure is already available. high-resolution structures can be rapidly created using only their sequence information as input, a process that has the potential to increase the speed of sc ...	2016	28119814
structure of the 40s ribosomal subunit of plasmodium falciparum by homology and de novo modeling.	generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary structures of organisms can be generated. this is especially the case if a homologous crystal structure is already available. high-resolution structures can be rapidly created using only their sequence information as input, a process that has the potential to increase the speed of sc ...	2016	28119814
pb(2+) effects on growth, lipids, and protein and dna profiles of the thermophilic bacterium thermus thermophilus.	extremophiles are organisms able to thrive in extreme environmental conditions and some of them show the ability to survive high doses of heavy metals thanks to defensive mechanisms provided by primary and secondary metabolic products, i.e., extremolytes, lipids, and extremozymes. this is why there is a growing scientific and industrial interest in the use of thermophilic bacteria in a host of tasks, from the environmental detoxification of heavy metal to industrial activities, such as bio-machi ...	2016	27929414
improved in-cell structure determination of proteins at near-physiological concentration.	investigating three-dimensional (3d) structures of proteins in living cells by in-cell nuclear magnetic resonance (nmr) spectroscopy opens an avenue towards understanding the structural basis of their functions and physical properties under physiological conditions inside cells. in-cell nmr provides data at atomic resolution non-invasively, and has been used to detect protein-protein interactions, thermodynamics of protein stability, the behavior of intrinsically disordered proteins, etc. in cel ...	2016	27910948
identification of a highly conserved hypothetical protein ton_0340 as a probable manganese-dependent phosphatase.	a hypothetical protein ton_0340 of a thermococcus species is a protein conserved in a variety of organisms including human. herein, we present four different crystal structures of ton_0340, leading to the identification of an active-site cavity harboring a metal-binding site composed of six invariant aspartate and glutamate residues that coordinate one to three metal ions. biochemical and mutational analyses involving many phosphorous compounds show that ton_0340 is a mn2+-dependent phosphatase. ...	2016	27907125
structures of type iv pilins from thermus thermophilus demonstrate similarities with type ii secretion system pseudopilins.	type iv pilins are proteins which form polymers that extend from the surface of the bacterial cell; they are involved in mediating a wide variety of functions, including adhesion, motility and natural competence. here we describe the determination of the crystal structures of three type iva pilins proteins from the thermophile thermus thermophilus. they form part of a cluster of pilus-like proteins within the genome; our results show that one, tt1222, is very closely related to the main structur ...	2016	27612581
structural basis for the disaggregase activity and regulation of hsp104.	the hsp104 disaggregase is a two-ring atpase machine that rescues various forms of non-native proteins including the highly resistant amyloid fibers. the structural-mechanistic underpinnings of how the recovery of toxic protein aggregates is promoted and how this potent unfolding activity is prevented from doing collateral damage to cellular proteins are not well understood. here, we present structural and biochemical data revealing the organization of hsp104 from chaetomium thermophilum at 3.7 ...	2016	27901467