Journal of Molecular Biology

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Substrate-Induced Allosteric Change in the Quaternary Structure of the Spermidine N-Acetyltransferase SpeG

Sun, 11/01/2015 - 22:48
Publication date: 6 November 2015
Source:Journal of Molecular Biology, Volume 427, Issue 22

Author(s): Ekaterina V. Filippova, Steven Weigand, Jerzy Osipiuk, Olga Kiryukhina, Andrzej Joachimiak, Wayne F. Anderson

The spermidine N-acetyltransferase SpeG is a dodecameric enzyme that catalyzes the transfer of an acetyl group from acetyl coenzyme A to polyamines such as spermidine and spermine. SpeG has an allosteric polyamine-binding site and acetylating polyamines regulate their intracellular concentrations. The structures of SpeG from Vibrio cholerae in complexes with polyamines and cofactor have been characterized earlier. Here, we present the dodecameric structure of SpeG from V. cholerae in a ligand-free form in three different conformational states: open, intermediate and closed. All structures were crystallized in C2 space group symmetry and contain six monomers in the asymmetric unit cell. Two hexamers related by crystallographic 2-fold symmetry form the SpeG dodecamer. The open and intermediate states have a unique open dodecameric ring. This SpeG dodecamer is asymmetric except for the one 2-fold axis and is unlike any known dodecameric structure. Using a fluorescence thermal shift assay, size-exclusion chromatography with multi-angle light scattering, small-angle X-ray scattering analysis, negative-stain electron microscopy and structural analysis, we demonstrate that this unique open dodecameric state exists in solution. Our combined results indicate that polyamines trigger conformational changes and induce the symmetric closed dodecameric state of the protein when they bind to their allosteric sites.
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Sequence–Structure–Function Classification of a Catalytically Diverse Oxidoreductase Superfamily in Mycobacteria

Sun, 11/01/2015 - 22:48
Publication date: 6 November 2015
Source:Journal of Molecular Biology, Volume 427, Issue 22

Author(s): F. Hafna Ahmed, Paul D. Carr, Brendon M. Lee, Livnat Afriat-Jurnou, A. Elaaf Mohamed, Nan-Sook Hong, Jack Flanagan, Matthew C. Taylor, Chris Greening, Colin J. Jackson

The deazaflavin cofactor F420 enhances the persistence of mycobacteria during hypoxia, oxidative stress, and antibiotic treatment. However, the identities and functions of the mycobacterial enzymes that utilize F420 under these conditions have yet to be resolved. In this work, we used sequence similarity networks to analyze the distribution of the largest F420-dependent protein family in mycobacteria. We show that these enzymes are part of a larger split β-barrel enzyme superfamily (flavin/deazaflavin oxidoreductases, FDORs) that include previously characterized pyridoxamine/pyridoxine-5′-phosphate oxidases and heme oxygenases. We show that these proteins variously utilize F420, flavin mononucleotide, flavin adenine dinucleotide, and heme cofactors. Functional annotation using phylogenetic, structural, and spectroscopic methods revealed their involvement in heme degradation, biliverdin reduction, fatty acid modification, and quinone reduction. Four novel crystal structures show that plasticity in substrate binding pockets and modifications to cofactor binding motifs enabled FDORs to carry out a variety of functions. This systematic classification and analysis provides a framework for further functional analysis of the roles of FDORs in mycobacterial pathogenesis and persistence.
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The Antibody Light-Chain Linker Is Important for Domain Stability and Amyloid Formation

Sun, 11/01/2015 - 22:48
Publication date: 6 November 2015
Source:Journal of Molecular Biology, Volume 427, Issue 22

Author(s): Cardine N. Nokwe, Manuel Hora, Martin Zacharias, Hisashi Yagi, Christine John, Bernd Reif, Yuji Goto, Johannes Buchner

The association of light chains (LCs) and heavy chains is the basis for functional antibodies that are essential for adaptive immune responses. However, in some cases, LCs and especially fragments consisting of the LC variable (VL) domain are pathologically deposited in fatal aggregation diseases. The two domains of the LC are connected by a highly conserved linker. We show here that, unexpectedly, the linker residue Arg108 affects the conformational stability and folding of both VLκ and LC constant (CLκ) domains. Interestingly, the extension of VL by Arg108 results in its resistance to amyloid formation, which suggests that the nature of the truncation of the LC plays a crucial role in disease progression. Increased solvation due to the exposed charged C-terminal Arg108 residue explains its stabilizing effects on the VL domain. For the CL domain, the interaction of N-terminal loop residues with Arg108 is important for the integrity of the domain, as the disruption of this interaction results in fluctuation, partial opening of the protein's interior and the exposure of hydrophobic residues that destabilize the domain. This establishes new principles for antibody domain architecture and amyloidogenicity.
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Effects of Linker Length and Transient Secondary Structure Elements in the Intrinsically Disordered Notch RAM Region on Notch Signaling

Sun, 11/01/2015 - 22:48
Publication date: 6 November 2015
Source:Journal of Molecular Biology, Volume 427, Issue 22

Author(s): Kathryn P. Sherry, Scott E. Johnson, Christine L. Hatem, Ananya Majumdar, Doug Barrick

Formation of the bivalent interaction between the Notch intracellular domain (NICD) and the transcription factor CBF-1/RBP-j, Su(H), Lag-1 (CSL) is a key event in Notch signaling because it switches Notch-responsive genes from a repressed state to an activated state. Interaction of the intrinsically disordered RBP-j-associated molecule (RAM) region of NICD with CSL is thought to both disrupt binding of corepressor proteins to CSL and anchor NICD to CSL, promoting interaction of the ankyrin domain of NICD with CSL through an effective concentration mechanism. To quantify the role of disorder in the RAM linker region on the effective concentration enhancement of Notch transcriptional activation, we measured the effects of linker length variation on activation. The resulting activation profile has general features of a worm-like chain model for effective concentration. However, deviations from the model for short sequence deletions suggest that RAM contains sequence-specific structural elements that may be important for activation. Structural characterization of the RAM linker with sedimentation velocity analytical ultracentrifugation and NMR spectroscopy reveals that the linker is compact and contains three transient helices and two extended and dynamic regions. To test if these secondary structure elements are important for activation, we made sequence substitutions to change the secondary structure propensities of these elements and measured transcriptional activation of the resulting variants. Substitutions to two of these nonrandom elements (helix 2, extended region 1) have effects on activation, but these effects do not depend on the nature of the substituting residues. Thus, the primary sequences of these elements, but not their secondary structures, are influencing signaling.
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Peptide Probes Reveal a Hydrophobic Steric Ratchet in the Anthrax Toxin Protective Antigen Translocase

Sun, 11/01/2015 - 22:48
Publication date: 6 November 2015
Source:Journal of Molecular Biology, Volume 427, Issue 22

Author(s): Jennifer M. Colby, Bryan A. Krantz

Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor and edema factor, into the host cytosol under the proton motive force. Protein translocation under a proton motive force is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between the lethal factor amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide-clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides, and while these steric interactions may make a peptide translocate poorly, in the context of folded domains, they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism.
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Functional Monomerization of a ClC-Type Fluoride Transporter

Sun, 11/01/2015 - 22:48
Publication date: 6 November 2015
Source:Journal of Molecular Biology, Volume 427, Issue 22

Author(s): Nicholas B. Last, Christopher Miller

Anion channels and antiporters of the ClC superfamily have been found to be exclusively dimeric in nature, even though each individual monomer contains the complete transport pathway. Here, we describe the destabilization through mutagenesis of the dimer interface of a bacterial F−/H+ antiporter, ClCF-eca. Several mutations that produce monomer/dimer equilibrium of the normally dimeric transporter were found, simply by shortening a hydrophobic side chain in some cases. One mutation, L376W, leads to a wholly monomeric variant that shows full activity. Furthermore, we discovered a naturally destabilized homologue, ClCF-rla, which undergoes partial monomerization in detergent without additional mutations. These results, in combination with the previous functional monomerization of the distant relative ClC-ec1, demonstrate that the monomer alone is the functional unit for several clades of the ClC superfamily.
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Protein–Protein Interfaces in Viral Capsids Are Structurally Unique

Sun, 11/01/2015 - 22:48
Publication date: 6 November 2015
Source:Journal of Molecular Biology, Volume 427, Issue 22

Author(s): Shanshan Cheng, Charles L. Brooks

Viral capsids exhibit elaborate and symmetrical architectures of defined sizes and remarkable mechanical properties not seen with cellular macromolecular complexes. Given the uniqueness of the higher-order organization of viral capsid proteins in the virosphere, we explored the question of whether the patterns of protein–protein interactions within viral capsids are distinct from those in generic protein complexes. Our comparative analysis involving a non-redundant set of 551 inter-subunit interfaces in viral capsids from VIPERdb and 20,014 protein–protein interfaces in non-capsid protein complexes from the Protein Data Bank found 418 generic protein–protein interfaces that share similar physicochemical patterns with some protein–protein interfaces in the capsid set, using the program PCalign we developed for comparing protein–protein interfaces. This overlap in the structural space of protein–protein interfaces is significantly small, with a p-value <0.0001, based on a permutation test on the total set of protein–protein interfaces. Furthermore, the generic protein–protein interfaces that bear similarity in their spatial and chemical arrangement with capsid ones are mostly small in size with fewer than 20 interfacial residues, which results from the relatively limited choices of natural design for small interfaces rather than having significant biological implications in terms of functional relationships. We conclude based on this study that protein–protein interfaces in viral capsids are non-representative of patterns in the smaller, more compact cellular protein complexes. Our finding highlights the design principle of building large biological containers from repeated, self-assembling units and provides insights into specific targets for antiviral drug design for improved efficacy.
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Conformational Transitions that Enable Histidine Kinase Autophosphorylation and Receptor Array Integration

Sun, 11/01/2015 - 22:48
Publication date: Available online 30 October 2015
Source:Journal of Molecular Biology

Author(s): Anna R. Greenswag, Alise Muok, Xiaoxiao Li, Brian R. Crane

During bacterial chemotaxis, transmembrane chemoreceptor arrays regulate autophosphorylation of the dimeric, histidine-kinase CheA. The five domains of CheA (P1-P5) each play a specific role in coupling receptor stimulation to CheA activity. Biochemical and x-ray scattering studies of thermostable CheA from Thermotoga maritima find that the His-containing substrate domain (P1) is sequestered by interactions that depend upon P1 of the adjacent subunit. Non-hydrolyzable ATP analogs (but not ATP nor ADP) release P1 from the protein core (domains P3P4P5) and increase its mobility. Detachment of both P1 domains, or removal of one within a dimer, increases net autophosphorylation substantially at physiological temperature (55°C). However, nearly all activity is lost without the dimerization domain (P3). The linker length between P1 and P3 dictates inter-subunit (trans) versus intra-subunit (cis) autophosphorylation; with the trans reaction requiring a minimum length of 47 residues. A new crystal structure of the most active dimerization-plus-kinase unit (P3P4) reveals trans-directing interactions between the tether connecting P3 to P2-P1 and the adjacent ATP-binding (P4) domain. The orientation of P4 relative to P3 in the P3P4 structure supports a planar CheA conformation that is required by membrane array models, and suggests that the ATP-lid of CheA may be poised to interact with receptors and coupling proteins. Collectively, these data suggest that the P1 domains are restrained in the off-state as a result of cross-subunit interactions. Perturbations at the nucleotide-binding pocket increase P1 mobility and access of the substrate His to P4-bound ATP.
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Identification and characterization of botulinum neurotoxin A substrate binding pockets and their re-engineering for human SNAP-23

Sun, 11/01/2015 - 22:48
Publication date: Available online 30 October 2015
Source:Journal of Molecular Biology

Author(s): Stefan Sikorra, Christa Litschko, Carina Müller, Nadine Thiel, Thierry Galli, Timo Eichner, Thomas Binz

Botulinum neurotoxins are highly potent bacterial proteins that block neurotransmitter release at the neuromuscular junction by cleaving SNAREs. However, their serotype A (BoNT/A) which cleaves synaptosomal associated protein of 25 kDa (SNAP-25) has also been an established pharmaceutical for treatment of medical conditions that rely on hyperactivity of cholinergic nerve terminals for 25 years. The expansion of its use to a variety of further medical conditions associated with hypersecretion components is prevented partly because the involved SNARE isoforms are not cleaved. Therefore, we examined by mutational analyses the reason for the resistance of human SNAP-23, an isoform of SNAP-25. We show that replacement of ten SNAP-23 residues with their SNAP-25 counterparts effects SNAP-25-like cleavability. Conversely, transfer of each of the replaced SNAP-23 residues to SNAP-25 drastically decreased the cleavability of SNAP-25. By means of the existing SNAP-25-toxin co-crystal structure, molecular dynamics simulations, and corroborative mutagenesis studies the appropriate binding pockets for these residues in BoNT/A were characterized. Systematic mutagenesis of two major BoNT/A binding pockets was conducted in order to adapt these pockets to corresponding amino acids of human SNAP-23. Human SNAP-23 cleaving mutants were isolated using a newly established yeast based screening system. This method may be useful for engineering novel BoNT/A pharmaceuticals for the treatment of diseases that rely on SNAP-23 mediated hypersecretion.
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The bacterial transcription termination factor Rho coordinates Mg2+ homeostasis with translational signals

Sun, 11/01/2015 - 22:48
Publication date: Available online 30 October 2015
Source:Journal of Molecular Biology

Author(s): Michelle A. Kriner, Eduardo A. Groisman

The bacterial protein Rho triggers transcription termination at the ends of many operons and when transcription and translation become uncoupled. In addition to these genome-wide activities, Rho implements regulation of specific genes by dictating whether RNA polymerase terminates transcription within the 5’ leader region or continues into the downstream coding region. Here, we report that the Mg2+ channel gene corA in Salmonella enterica serovar Typhimurium, which was previously thought to be constitutively expressed, is regulated by a Rho-dependent terminator located within its 5’ leader region. We demonstrate that the unusually long and highly conserved corA leader mRNA can adopt two mutually exclusive conformations that determine whether or not Rho interacts with a Rho utilization (rut) site on the nascent RNA and thereby prevents transcription of the corA coding region. The RNA conformation that promotes Rho-dependent termination is favored by efficient translation of corL, a short open reading frame located within the corA leader. Thus, corA transcription is inversely coupled to corL translation. This mechanism resembles those governing expression of Salmonella’s other two Mg2+ transport genes, suggesting that Rho links Mg2+ uptake to translational signals.
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Structural biology and regulation of protein import into the nucleus

Sun, 11/01/2015 - 22:48
Publication date: Available online 30 October 2015
Source:Journal of Molecular Biology

Author(s): Mary Christie, Chiung-Wen Chang, Gergely Róna, Kate M. Smith, Alastair G. Stewart, Agnes A.S. Takeda, Marcos R.M. Fontes, Murray Stewart, Beáta G. Vértessy, Jade K. Forwood, Bostjan Kobe

Proteins are translated in the cytoplasm, but many need to access the nucleus to perform their functions. Understanding how these nuclear proteins are transported through the nuclear envelope and how the import processes are regulated is therefore an important aspect of understanding cell function. Structural biology has played a key role in understanding the molecular events during the transport processes and their regulation, including the recognition of nuclear targeting signals by the corresponding receptors. Here, we review the structural basis of the principal nuclear import pathways and the molecular basis of their regulation. The pathways involve transport factors that are members of the β-karyopherin family, which can bind cargo directly (e.g. importin-β, transportin-1, transportin-3, importin-13) or through adaptor proteins (e.g. importin-α, snurportin-1, symportin-1), as well as unrelated transport factors such as Hikeshi, involved in the transport of heat-shock proteins, and NTF2, involved in the transport of RanGDP. Solenoid proteins feature prominently in these pathways. Nuclear transport factors recognize nuclear targeting signals on the cargo proteins, including the classical nuclear localization signals (cNLSs), recognized by the adaptor importin-α, and the PY-NLSs, recognized by transportin-1. Post-translational modifications, in particular phosphorylation, constitute key regulatory mechanisms operating in these pathways.
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Base flipping by MTERF1 can accommodate multiple conformations and occurs in a stepwise fashion

Sun, 11/01/2015 - 22:48
Publication date: Available online 30 October 2015
Source:Journal of Molecular Biology

Author(s): James Byrnes, Kevin Hauser, Leah Norona, Edison Mejia, Carlos Simmerling, Miguel Garcia-Diaz

Human mitochondrial transcription termination occurs within the leu-tRNA gene and is mediated by the DNA binding protein MTERF1. The crystal structure of MTERF1 bound to the canonical termination sequence reveals a rare base flipping event that involves the eversion of three nucleotides. These nucleotides are stabilized by stacking interactions with three MTERF1 residues, which are not only essential for base flipping but also for termination activity. To further understand the mechanism of base flipping we examined each of the individual stacking interactions in structural, energetic and functional detail. Individual substitutions of Arg162, Tyr288 and Phe243 have revealed unequal contributions to overall termination activity. Furthermore, our work identifies an important role for Phe322 in the base flipping mechanism and we demonstrate how Phe322 and Phe243 are important for coupling base flipping between the heavy and light strand DNA chains. We propose a step-wise model for the base flipping process that recapitulates our observations. Finally, we show that MTERF1 has the ability to accommodate alternate active conformations. The adaptability of base flipping has implications for MTERF1 function and for the putative function of MTERF1 at alternative binding sites in human mitochondria.





Categories: Journal Articles

Determination of Protein Folding Intermediate Structures Consistent with Data from Oxidative Footprinting Mass Spectrometry

Sun, 11/01/2015 - 22:48
Publication date: Available online 30 October 2015
Source:Journal of Molecular Biology

Author(s): Florian Heinkel, Jörg Gsponer

The mapping of folding landscapes remains an important challenge in protein chemistry. Pulsed oxidative labeling of exposed residues and their detection via mass spectrometry provides new means of taking time-resolved “snapshots” of the structural changes that occur during protein folding. However, such experiments have so far only been interpreted qualitatively. Here, we report the detailed structural interpretation of mass spectrometry data from fast photochemical oxidation of proteins (FPOP) experiments at atomic resolution in a biased molecular dynamics approach. We are able to calculate structures of the early folding intermediate of the model system barstar that are fully consistent with FPOP data as well as Φ values. Furthermore, structures calculated with both FPOP data and Φ values are significantly less compact and have fewer helical residues than intermediate structures calculated with Φ values only. This improves the agreement with the experimental β-Tanford value as well as CD measurements. The restraints that we introduce facilitate the structural interpretation of FPOP data and provide new means for refined structure calculations of transiently samples states on protein folding landscapes.
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The kink-turn, a key architectural element in RNA structure

Sun, 11/01/2015 - 22:48
Publication date: Available online 29 October 2015
Source:Journal of Molecular Biology

Author(s): Lin Huang, David M.J. Lilley

Kink-turns (k-turns) are widespread structural elements that introduce an axial bend into duplex RNA with an included angle of 50°. These mediate key tertiary interactions, and bind specific proteins including members of the L7Ae family. The standard k-turn comprises a three-nucleotide bulge followed by G•A and A•G pairs. The RNA kinks by an association of the two minor grooves, stabilized by the formation of a number of key cross-strand hydrogen bonds mostly involving the adenine bases of the G•A and A•G pairs. The k-turns may be divided into two conformational classes, depending on the receptor for one of these hydrogen bonds. k-turns become folded by one of three different processes. Some, but not all, k-turns become folded in the present of metal ions. Whether or not a given k-turn is folded under these conditions is determined by its sequence. We present a set of rules for the prediction of folding properties, and the structure adopted, on local sequence.
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Breaching the barrier - the nuclear envelope in virus infection

Sun, 11/01/2015 - 22:48
Publication date: Available online 29 October 2015
Source:Journal of Molecular Biology

Author(s): Thomas C. Mettenleiter

Many DNA and a few RNA viruses use the host cell nucleus for virion formation and/or genome replication. To this end, the nuclear envelope barrier has to be overcome for entry into and egress from the intranuclear replication compartment. Different virus families have devised ingenious ways of entering and leaving the nucleus usurping cellular transport pathways through the nuclear pore complex but also translocating directly through both membranes of the nuclear envelope. This intriguing diversity in nuclear entry and egress of viruses also highlights different ways nucleo-cytoplasmic transport can occur. Thus, the study of interactions between viruses and the nuclear envelope also helps to unravel hitherto unknown cellular pathways such as vesicular nucleo-cytoplasmic transfer.
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Mechanistic insights from structural analyses of Ran GTPase-driven nuclear export of proteins and RNAs

Sun, 11/01/2015 - 22:48
Publication date: Available online 28 October 2015
Source:Journal of Molecular Biology

Author(s): Yoshiyuki Matsuura

Understanding how macromolecules are rapidly exchanged between the nucleus and the cytoplasm through nuclear pore complexes (NPCs) is a fundamental problem in biology. Exportins are Ran GTPase-dependent nuclear transport factors that belong to the karyopherin-β family and mediate nuclear export of a plethora of proteins and RNAs, except for bulk mRNA nuclear export. Exportins bind cargo macromolecules in a Ran-GTP dependent manner in the nucleus, forming exportin-cargo-Ran-GTP complexes (nuclear export complexes). Transient weak interactions between exportins and nucleoporins containing characteristic phenylalanine-glycine (FG) repeat motifs facilitate NPC passage of nuclear export complexes. In the cytoplasm, nuclear export complexes are disassembled, thereby releasing the cargo. GTP hydrolysis by Ran promoted in the cytoplasm makes the disassembly reaction virtually irreversible and provides thermodynamic driving force for the overall export reaction. In the past decade, X-ray crystallography of some of the exportins in various functional states coupled with functional analyses, single particle electron microscopy, molecular dynamics simulations, and small-angle solution X-ray scattering has provided rich insights into the mechanism of cargo binding and release, and also beginning to elucidate how exportins interact with the FG repeat motifs. The knowledge gained from structural analyses of nuclear export is being translated into development of clinically useful inhibitors of nuclear export to treat human diseases such as cancer and influenza.
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Intermicrobial interactions as a driver for community composition and stratification of oral biofilms

Sun, 11/01/2015 - 22:48
Publication date: Available online 28 October 2015
Source:Journal of Molecular Biology

Author(s): Nicholas S. Jakubovics

The oral cavity is accessible to microorganisms, and biofilms are present throughout on hard and soft tissues. The shedding of epithelial cell layers is usually effective for controlling biofilm development on soft tissues. Innate immune mechanisms are not so effective against biofilms on tooth surfaces, and oral hygiene measures such as brushing and flossing are required for the periodic removal of dental plaque. Even with good oral hygiene, microbial communities accumulate on teeth in areas that are protected from mechanical abrasion forces. Changes in the composition of these biofilms are associated with oral diseases such as dental caries or periodontitis. Newly formed biofilms and more mature dental plaque each have a level of spatial organization in the horizontal and vertical planes. Communities are shaped by many varied interactions between different species and genera within the biofilm, which include physical cell-cell associations known as coaggregation, interspecies signaling, secretion and turnover of antimicrobial compounds, and the sharing of an extracellular matrix. Central to these interactions is the selection for metabolic synergies and it is becoming clear that the ability of communities to extract the maximum energy from the available metabolites is a potent driver for biofilm structure and stratification. This review discusses recent advances in our understanding of intermicrobial interactions in oral biofilms and the roles that they play in determining the spatial organization of biofilm communities.
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PhyreStorm: A web server for fast structural searches against the PDB

Sun, 11/01/2015 - 22:48
Publication date: Available online 27 October 2015
Source:Journal of Molecular Biology

Author(s): Stefans Mezulis, Michael J.E. Sternberg, Lawrence A. Kelley

The identification of structurally similar proteins can provide a range of biological insights and accordingly the alignment of a query protein to a database of experimentally-determined protein structures is a technique commonly used in the fields of structural and evolutionary biology. The PhyreStorm web server has been designed to provide comprehensive, up-to-date and rapid structural comparisons against the Protein Data Bank (PDB) combined with a rich and intuitive user interface. It is intended that this facility will enable biologists inexpert in bioinformatics access to a powerful tool for exploring protein structure relationships beyond what can be achieved by sequence analysis alone. By partitioning the PDB into similar structures, PhyreStorm is able to quickly discard the majority of structures that cannot possibly align well to a query protein, reducing the number of alignments required by an order of magnitude. PhyreStorm is capable of finding 93±2% of all highly similar (TM-score >0.7) structures in the PDB for each query structure, usually in under 60 seconds. PhyreStorm is available at http://www.sbg.bio.ic.ac.uk/phyrestorm/
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A Snapshot of the Extraordinary World of Social Microbiology

Sun, 11/01/2015 - 22:48
Publication date: Available online 27 October 2015
Source:Journal of Molecular Biology

Author(s): Nicola R. Stanley-Wall, Sarah J. Coulthurst, Ian Barry Holland







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Bacterial Networks in Cells and Communities

Sun, 11/01/2015 - 22:48
Publication date: Available online 24 October 2015
Source:Journal of Molecular Biology

Author(s): Victor Sourjik, Julia A. Vorholt

Research on the bacterial regulatory networks is currently experiencing a true revival, driven by advances in methodology and by emergence of novel concepts. The biannual conference Bacterial Networks (BacNet15) held in May 2015, in Sant Feliu de Guíxols, Spain, covered progress in the studies of regulatory networks that control bacterial physiology, cell biology, stress responses, metabolism, collective behavior and evolution. It demonstrated how interdisciplinary approaches that combine molecular biology and biochemistry with the latest microscopy developments, whole cell (−omics) approaches and mathematical modeling can help understand design principles relevant in microbiology. It further showed how current biotechnology and medical microbiology could profit from our knowledge of and ability to engineer regulatory networks of bacteria.
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Categories: Journal Articles