The Mechanisms of Substrate Selection, Catalysis, and Translocation by the Elongating RNA Polymerase
Publication date: Available online 31 May 2019Source: Journal of Molecular BiologyAuthor(s): Georgiy A. Belogurov, Irina ArtsimovitchAbstractMulti-subunit DNA-dependent RNA polymerases synthesize all classes of cellular RNAs, ranging from short regulatory transcripts to gigantic messenger RNAs. RNA polymerase has to make each RNA product in just one try, even if it takes millions of successive nucleotide addition steps. During each step, RNA polymerase selects a correct substrate, adds it to a growing chain, and moves one nucleotide forward before repeating the cycle. However, RNA synthesis is anything but monotonous: RNA ...
Source: Journal of Molecular Biology - June 20, 2019 Category: Molecular Biology Source Type: research

Outside Front Cover
Publication date: 28 June 2019Source: Journal of Molecular Biology, Volume 431, Issue 14Author(s): (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - June 20, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 28 June 2019Source: Journal of Molecular Biology, Volume 431, Issue 14Author(s): (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - June 20, 2019 Category: Molecular Biology Source Type: research

Transcription-Coupled Repair: From Cells to Single Molecules and Back Again
Publication date: Available online 6 June 2019Source: Journal of Molecular BiologyAuthor(s): T.R. Strick, J.R. PortmanAbstractTranscription-coupled repair is mediated by the Mfd protein. TCR is defined as the preferential repair of DNA lesions in the transcribed strand of actively transcribed genes, and is opposed to the strand-aspecific global genome repair. The Mfd protein mediates TCR by binding to and displacing RNA polymerase, which is stalled at a DNA lesion on the transcribed strand of DNA, then recruiting UvrA and UvrB. The repair cascade results in the recruitment of, and DNA excision by, UvrC; removal of the dama...
Source: Journal of Molecular Biology - June 19, 2019 Category: Molecular Biology Source Type: research

Outside Front Cover
Publication date: 14 June 2019Source: Journal of Molecular Biology, Volume 431, Issue 13Author(s): (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - June 19, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 14 June 2019Source: Journal of Molecular Biology, Volume 431, Issue 13Author(s): (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - June 19, 2019 Category: Molecular Biology Source Type: research

Jekyll and Hyde: Bugs with Double Personalities that Muddle the Distinction between Commensal and Pathogen
Publication date: Available online 18 June 2019Source: Journal of Molecular BiologyAuthor(s): John R. Brannon, Matthew A. Mulvey (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - June 19, 2019 Category: Molecular Biology Source Type: research

CHAP: A Versatile Tool for the Structural and Functional Annotation of Ion Channel Pores
Publication date: Available online 17 June 2019Source: Journal of Molecular BiologyAuthor(s): Gianni Klesse, Shanlin Rao, Mark S.P. Sansom, Stephen J. TuckerAbstractThe control of ion channel permeation requires the modulation of energetic barriers or “gates” within their pores. However, such barriers are often simply identified from the physical dimensions of the pore. Such approaches have worked well in the past,but there is now evidence that the unusual behaviour of water within narrow hydrophobic pores can produce an energetic barrier to permeation without requiring steric occlusion of the pathway. Many dif...
Source: Journal of Molecular Biology - June 18, 2019 Category: Molecular Biology Source Type: research

Cell Heterogeneity in Staphylococcal Communities
Publication date: Available online 17 June 2019Source: Journal of Molecular BiologyAuthor(s): Juan Carlos García-Betancur, Daniel LopezAbstractThe human pathogen Staphylococcus aureus is a Gram-positive bacterium that causes difficult-to-treat infections. One of the reasons why S. aureus is such as successful pathogen is due to the cell-to-cell physiological variability that exists within microbial communities. Many laboratories around the world study the genetic mechanisms involved in S. aureus cell heterogeneity to better undertand infection mechanism of this bacterium. It was recently shown that the Agr quorum-se...
Source: Journal of Molecular Biology - June 18, 2019 Category: Molecular Biology Source Type: research

Physiological Stress Response by Selective Autophagy
Publication date: Available online 18 June 2019Source: Journal of Molecular BiologyAuthor(s): Pablo Sánchez-Martín, Masaaki KomatsuAbstractCells are constantly challenged by endogenous and exogenous stress sources. To cope with them, organisms have developed a series of defensive mechanism to prevent and intercept the threats and to repair the generated damage. Autophagy, once defined as a waste-disposal or non-specific degradative pathway, has arisen as a new organizer of the different physiological stress responses. In the present review we will discuss how autophagy is capable of orchestrate these pathways...
Source: Journal of Molecular Biology - June 18, 2019 Category: Molecular Biology Source Type: research

The Arginines in the N-Terminus of the Porcine Circovirus 2 Virus-like Particles Are Responsible for Disrupting the Membranes at Neutral and Acidic pH
We describe an additional mechanism by a non-enveloped virus to disrupt endosomal membranes. Porcine circovirus 2 (PCV2) possesses a 41-amino acid arginine-rich motif (ARM) at the N-terminus of its capsid protein that appears to be in the interior of the virus-like particle (VLP). Using in vitro membrane disruption assays, we demonstrate that PCV2 VLP, unassembled capsid, and ARM peptide possess the ability to disrupt endosomal-like membranes, whereas VLP lacking the ARM sequence does not possess this capability. Membrane disruption by VLP is insensitive to pH, but unassembled capsid protein and ARM peptide exhibit diminis...
Source: Journal of Molecular Biology - June 18, 2019 Category: Molecular Biology Source Type: research

The Phosphatase PRL-3 Is Involved in Key Steps of Cancer Metastasis
Publication date: Available online 14 June 2019Source: Journal of Molecular BiologyAuthor(s): Laura Duciel, Luis Cristobal Monraz Gomez, Maria Kondratova, Inna Kuperstein, Simon SauleAbstractPRL-3 belongs to the PRL phosphatase family. Its physiological role remains unclear, but many studies have identified PRL-3 is a marker of cancer progression and shown it to be associated with metastasis. Evidence implicating PRL-3 in various elements of the metastatic process, such as the cell cycle, survival, angiogenesis, adhesion, cytoskeleton remodelling, EMT, motility and invasion has been reported. Furthermore, several molecules...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

Predicting Protein–Protein Interfaces that Bind Intrinsically Disordered Protein Regions
Publication date: Available online 15 June 2019Source: Journal of Molecular BiologyAuthor(s): Eric T.C. Wong, Jörg GsponerAbstractA long-standing goal in biology is the complete annotation of function and structure on all protein–protein interactions, a large fraction of which is mediated by intrinsically disordered protein regions (IDRs). However, our knowledge base of experimentally derived structures of such protein complexes is disproportionately small, partly due to challenges in studying interactions of IDRs. Here, we introduce IDRBind, a computational method that by combining gradient boosted trees and co...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

CRISPR/Cas9-based knockout strategy elucidates components essential for type 1 interferon signaling in human HeLa cells
Publication date: Available online 15 June 2019Source: Journal of Molecular BiologyAuthor(s): Victoria Urin, Maya Shemesh, Gideon SchreiberAbstractType I interferons (IFNs) have a central role in innate and adaptive immunities, proliferation, and cancer surveillance. How IFN binding to its specific receptor, the interferon α and β receptor (IFNAR), can drive such variety of processes is an open question. Here, to systematically and thoroughly investigate the molecular mechanism of IFN signaling, we used a CRISPR/Cas9-based approach in a human cell line (HeLa) to generate knockouts (KOs) of the genes participatin...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

A Single-Molecule View of Archaeal Transcription
Publication date: Available online 15 June 2019Source: Journal of Molecular BiologyAuthor(s): Kevin Kramm, Ulrike Endesfelder, Dina GrohmannAbstractThe discovery of the archaeal domain of life is tightly connected to an in depth analysis of the prokaryotic RNA world. In addition to Carl Woese's approach to use the sequence of the 16S rRNA gene as phylogenetic marker, the finding of Karl Stetter and Wolfram Zillig that archaeal RNA polymerases were nothing like the bacterial RNA polymerase (RNAP) but are more complex enzymes that resemble the eukaryotic RNAPII was one of the key findings supporting the idea that archaea con...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

Structure-Guided Generation of a Redox-Independent Blue Fluorescent Protein from mBFP
Publication date: Available online 13 June 2019Source: Journal of Molecular BiologyAuthor(s): Pil-Won Seo, Eun-Seo Jo, Sung-Hwan You, Dae-Eun Cheong, Geun-Joong Kim, Jeong-Sun KimAbstractFluorescent proteins, such as the green fluorescent protein (GFP), are used for detection of cellular components and events. However, GFP and its derivatives have limited usage under anaerobic conditions and require a long maturation time. On the other hand, the NADPH-dependent blue fluorescent protein (BFP) without oxidative modification of residues is instantly functional in both aerobic and anaerobic systems. BFP proteins belong to a sh...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

Conformational Cycling within the Closed State of Grp94, an Hsp90-Family Chaperone
Publication date: Available online 14 June 2019Source: Journal of Molecular BiologyAuthor(s): Bin Huang, Larry J. Friedman, Ming Sun, Jeff Gelles, Timothy O. StreetAbstractThe Hsp90 family of chaperones require ATP-driven cycling to perform their function. The presence of two bound ATP molecules is known to favor a closed conformation of the Hsp90 dimer. However, the structural and mechanistic consequences of subsequent ATP hydrolysis are poorly understood. Using single molecule FRET we discover novel dynamic behavior in the closed state of Grp94, the Hsp90 family member resident in the endoplasmic reticulum. Under ATP tur...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

Crystal Structure of the YcjX Stress Protein Reveals a Ras-Like GTP-Binding Protein
Publication date: Available online 14 June 2019Source: Journal of Molecular BiologyAuthor(s): Joshua T. Tsai, Nuri Sung, Jungsoon Lee, Changsoo Chang, Sukyeong Lee, Francis T.F. TsaiAbstractStress proteins promote cell survival by monitoring protein homeostasis in cells and organelles. YcjX is a conserved protein of unknown function, which is highly upregulated in response to acute and chronic stress. Notably, heat shock induction of ycjX exceeded even levels observed for major stress-induced chaperones, including GroEL, ClpB, and HtpG which use ATP as energy source. YcjX features a Walker-type nucleotide-binding domain in...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

Lipids and lipid-binding proteins in selective autophagy
Publication date: Available online 14 June 2019Source: Journal of Molecular BiologyAuthor(s): Laura R. de la Ballina, Michael J. Munson, Anne SimonsenAbstractEukaryotic cells have the capacity to degrade intracellular components through a lysosomal degradation pathway called macroautophagy (henceforth referred to as autophagy) in which superfluous or damaged cytosolic entities are engulfed and separated from the rest of the cell constituents into double membraned vesicles known as autophagosomes. Autophagosomes then fuse with endosomes and lysosomes, where cargo is broken down into basic building blocks that are released t...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

Mechanisms of non-segmented negative sense RNA viral antagonism of host RIG-I-like receptors
Publication date: Available online 14 June 2019Source: Journal of Molecular BiologyAuthor(s): Daisy W. LeungAbstractThe pattern recognition receptors RIG-I-like receptors (RLRs) are critical molecules for cytosolic viral recognition and for subsequent activation of Type I interferon (IFN) production. The IFN signaling pathway plays a key role in viral detection and generating antiviral responses. Among the many pathogens, the non-segmented negative sense RNA viruses (NNSVs) target the RLR pathway using a variety of mechanisms. Here, I review the current state of knowledge on the molecular mechanisms that allow NNSV recogni...
Source: Journal of Molecular Biology - June 15, 2019 Category: Molecular Biology Source Type: research

RGS6 and RGS7 Discriminate between the Highly Similar Gαi and Gαo Proteins Using a Two-Tiered Specificity Strategy
Publication date: Available online 30 May 2019Source: Journal of Molecular BiologyAuthor(s): Ran Israeli, Ali Asli, Meirav Avital-Shacham, Mickey KosloffAbstractRGS6 and RGS7 are regulators of G protein signaling (RGS) proteins that inactivate heterotrimeric (αβγ) G proteins and mediate diverse biological functions, such as cardiac and neuronal signaling. Uniquely, both RGS6 and RGS7 can discriminate between Gαo and Gαi1—two similar Gα subunits that belong to the same Gi sub-family. Here, we show that the isolated RGS domains of RGS6 and RGS7 are sufficient to achieve this specifici...
Source: Journal of Molecular Biology - June 12, 2019 Category: Molecular Biology Source Type: research

Dr. Jekyll and Mr. Hide: How Enterococcus faecalis Subverts the Host Immune Response to Cause Infection
Publication date: Available online 25 May 2019Source: Journal of Molecular BiologyAuthor(s): Patrick Hsien Neng Kao, Kimberly A. KlineAbstractEnterococcus faecalis, a ubiquitous member of the healthy human gut microbiota, is also a common opportunistic pathogen and leading cause of nosocomial infections. This tenacious microbe is well adapted to infect and persist in multiple niches within the mammalian host and can rapidly tune its metabolism to respond to new environments, enabling infection in sites including the gastrointestinal tract, urinary tract, wounded epithelium, heart, and blood. In order to withstand and persi...
Source: Journal of Molecular Biology - June 11, 2019 Category: Molecular Biology Source Type: research

Transcription Regulators in Archaea: Homologies and Differences with Bacterial Regulators
Publication date: Available online 11 June 2019Source: Journal of Molecular BiologyAuthor(s): Liesbeth Lemmens, Hassan Ramadan Maklad, Indra Bervoets, Eveline PeetersAbstractThe fitness and survival of prokaryotic microorganisms depends on their ability to adequately respond to environmental changes, sudden stress conditions and metabolic shifts. An important mechanism underlying this response is the regulation of gene expression mediated by transcription factors that are responsive to small-molecule ligands or other intracellular signals. Despite constituting a distinct domain of life from bacteria and harboring a eukaryo...
Source: Journal of Molecular Biology - June 11, 2019 Category: Molecular Biology Source Type: research

Ribosome Abundance Control Via the Ubiquitin-Proteasome System and Autophagy
Publication date: Available online 11 June 2019Source: Journal of Molecular BiologyAuthor(s): Heeseon An, J. Wade HarperAbstractRibosomes are central to the life of a cell, as they translate the genetic code into the amino acid language of proteins. Moreover, ribosomal abundance within the cell is coordinated with protein production required for cell function or processes such as cell division. As such, it is not surprising that these elegant machines are both highly regulated at the level of both their output of newly translated proteins but also at the level of ribosomal protein expression, ribosome assembly, and ribosom...
Source: Journal of Molecular Biology - June 11, 2019 Category: Molecular Biology Source Type: research

Tol Energy-Driven Localization of Pal and Anchoring to the Peptidoglycan Promote Outer-Membrane Constriction
Publication date: Available online 31 May 2019Source: Journal of Molecular BiologyAuthor(s): Mélissa Petiti, Bastien Serrano, Laura Faure, Roland Lloubes, Tâm Mignot, Denis DuchéAbstractDuring cell division, gram-negative bacteria must coordinate inner-membrane invagination, peptidoglycan synthesis and cleavage and outer-membrane (OM) constriction. The OM constriction remains largely enigmatic, and the nature of this process, passive or active, is under debate. The proton-motive force-dependent Tol–Pal system performs a network of interactions within these three compartments. Here we confirm that ...
Source: Journal of Molecular Biology - June 9, 2019 Category: Molecular Biology Source Type: research

Dynamic Properties of Human α-Synuclein Related to Propensity to Amyloid Fibril Formation
Publication date: Available online 8 June 2019Source: Journal of Molecular BiologyAuthor(s): Satoru Fujiwara, Fumiaki Kono, Tatsuhito Matsuo, Yasunobu Sugimoto, Tomoharu Matsumoto, Akihiro Narita, Kaoru ShibataAbstractα-synuclein (αSyn) is an intrinsically disordered protein (IDP) that can form amyloid fibrils. Fibrils of αSyn are implicated with the pathogenesis of Parkinson's disease and other synucleinopathies. Elucidating the mechanism of fibril formation of αSyn is therefore important for understanding the mechanism of the pathogenesis of these diseases. Fibril formation of αSyn is sensit...
Source: Journal of Molecular Biology - June 8, 2019 Category: Molecular Biology Source Type: research

Structural Polymorphism of Actin
Publication date: Available online 8 June 2019Source: Journal of Molecular BiologyAuthor(s): Toshiro Oda, Shuichi Takeda, Akihiro Narita, Yuichiro MaédaAbstractInformation on the structural polymorphism of a protein is essential to understand the mechanisms of how it functions at an atomic level. Numerous studies on actin have accumulated substantial amounts of information about its polymorphism and there are over 200 published atomic structures of different forms of actin using crystallography, fiber diffraction, and electron microscopy. To characterize all the reported structures, we proposed simple parameters bas...
Source: Journal of Molecular Biology - June 8, 2019 Category: Molecular Biology Source Type: research

The Cytoplasm-Entry Domain of Antibacterial CdiA Is a Dynamic α-Helical Bundle with Disulfide-Dependent Structural Features
Publication date: Available online 8 June 2019Source: Journal of Molecular BiologyAuthor(s): Nicholas L. Bartelli, Sheng Sun, Grant C. Gucinski, Hongjun Zhou, Kiho Song, Christopher S. Hayes, Frederick W. DahlquistAbstractMany Gram-negative bacterial species use contact-dependent growth inhibition (CDI) systems to compete with neighboring cells. CDI+ strains express cell-surface CdiA effector proteins, which carry a toxic C-terminal region (CdiA-CT) that is cleaved from the effector upon transfer into the periplasm of target bacteria. The released CdiA-CT consists of two domains. The C-terminal domain is typically a nuclea...
Source: Journal of Molecular Biology - June 8, 2019 Category: Molecular Biology Source Type: research

The Microbial Toxin Microcin B17: Prospects for the Development of New Antibacterial Agents
Publication date: Available online 8 June 2019Source: Journal of Molecular BiologyAuthor(s): Frederic Collin, Anthony MaxwellAbstractMicrocin B17 (MccB17) is an antibacterial peptide produced by strains of Escherichia coli harbouring the plasmid-borne mccB17 operon. MccB17 possesses many notable features. It is able to stabilise the transient DNA gyrase-DNA cleavage complex, a very efficient mode of action shared with the highly-successful fluoroquinolone drugs. MccB17 stabilises this complex by a distinct mechanism making it potentially valuable in the fight against bacterial antibiotic resistance. MccB17 was the first co...
Source: Journal of Molecular Biology - June 8, 2019 Category: Molecular Biology Source Type: research

Transcription-Coupled Repair: From Cells to Single-Molecules and Back Again
Publication date: Available online 6 June 2019Source: Journal of Molecular BiologyAuthor(s): T.R. Strick, J.R. PortmanAbstractTranscription-coupled repair is mediated by the Mfd protein. TCR is defined as the preferential repair of DNA lesions in the transcribed strand of actively transcribed genes, and is opposed to the strand aspecific global genome repair. The Mfd protein mediates TCR by binding to and displacing RNA polymerase which is stalled at a DNA lesion on the transcribed strand of DNA, then recruiting UvrA and UvrB. The repair cascade results in the recruitment of, and DNA excision by, UvrC; removal of the damag...
Source: Journal of Molecular Biology - June 6, 2019 Category: Molecular Biology Source Type: research

Computation Resources for Molecular Biology: Special Issue 2019
Publication date: Available online 30 May 2019Source: Journal of Molecular BiologyAuthor(s): Boris Lenhard, Michael J.E. Sternberg (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - June 5, 2019 Category: Molecular Biology Source Type: research

Outside Front Cover
Publication date: 31 May 2019Source: Journal of Molecular Biology, Volume 431, Issue 12Author(s): (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - June 5, 2019 Category: Molecular Biology Source Type: research

Crystal Structure of Dihydro-Heme d1 Dehydrogenase NirN from Pseudomonas aeruginosa Reveals Amino Acid Residues Essential for Catalysis
Publication date: Available online 4 June 2019Source: Journal of Molecular BiologyAuthor(s): Thomas Klünemann, Arne Preuß, Julia Adamczack, Luis F.M. Rosa, Falk Harnisch, Gunhild Layer, Wulf BlankenfeldtAbstractMany bacteria can switch from oxygen to nitrogen oxides, such as nitrate or nitrite, as terminal electron acceptors in their respiratory chain. This process is called ‘denitrification’ and enables biofilm formation of the opportunistic human pathogen Pseudomonas aeruginosa, making it more resilient to antibiotics and highly adaptable to different habitats. The reduction of nitrite to nitric ox...
Source: Journal of Molecular Biology - June 5, 2019 Category: Molecular Biology Source Type: research

The Arginines in the N-Terminus of the Porcine Circovirus 2 Virus like Particles Are Responsible for Disrupting the Membranes at Neutral and Acidic pH
We describe an additional mechanism by a non-enveloped virus to disrupt endosomal membranes. Porcine Circovirus 2 (PCV2), possesses a forty-one amino acid arginine rich motif (ARM) at the N-terminus of its capsid protein that appears to be in the interior of the virus like particle (VLP). Using in-vitro membrane disruption assays we demonstrate that PCV2 VLP, unassembled capsid, and ARM peptide possess the ability to disrupt endosomal like membranes, whereas VLP lacking the ARM sequence do not possess this capability. Membrane disruption by VLP is insensitive to pH, but unassembled capsid protein and ARM peptide exhibit di...
Source: Journal of Molecular Biology - June 5, 2019 Category: Molecular Biology Source Type: research

Interaction of the Mechanosensitive Channel, MscS, with the Membrane Bilayer through Lipid Intercalation into Grooves and Pockets
Publication date: Available online 4 June 2019Source: Journal of Molecular BiologyAuthor(s): Tim Rasmussen, Akiko Rasmussen, Limin Yang, Corinna Kaul, Susan Black, Heloisa Galbiati, Stuart J. Conway, Samantha Miller, Paul Blount, Ian Rylance BoothAbstractAll membrane proteins have dynamic and intimate relationships with the lipids of the bilayer that may determine their activity. Mechanosensitive channels sense tension through their interaction with the lipids of the membrane. We have proposed a mechanism for the bacterial channel of small conductance, MscS, that envisages variable occupancy of pockets in the channel by li...
Source: Journal of Molecular Biology - June 5, 2019 Category: Molecular Biology Source Type: research

Elucidating Relayed Proton Transfer through a His–Trp–His Triad of a Transmembrane Proton Channel by Solid-State NMR
Publication date: Available online 11 May 2019Source: Journal of Molecular BiologyAuthor(s): Byungsu Kwon, Matthias Roos, Venkata S. Mandala, Alexander A. Shcherbakov, Mei HongAbstractProton transfer through membrane-bound ion channels is mediated by both water and polar residues of proteins, but the detailed molecular mechanism is challenging to determine. The tetrameric influenza A and B virus M2 proteins form canonical proton channels that use an HxxxW motif for proton selectivity and gating. The BM2 channel also contains a second histidine (His), H27, equidistant from the gating tryptophan, which leads to a symmetric H...
Source: Journal of Molecular Biology - June 5, 2019 Category: Molecular Biology Source Type: research

Docking on Lipid II—A Widespread Mechanism for Potent Bactericidal Activities of Antibiotic Peptides
Publication date: Available online 14 May 2019Source: Journal of Molecular BiologyAuthor(s): Fabian Grein, Tanja Schneider, Hans-Georg SahlAbstractNatural product antibiotics usually target the major biosynthetic pathways of bacterial cells and the search for new targets outside these pathways has proven very difficult. Cell wall biosynthesis maybe the most prominent antibiotic target, and ß-lactams are among the clinically most relevant antibiotics. Among cell wall biosynthesis inhibitors, glycopeptide antibiotics are a second group of important drugs, which bind to the peptidoglycan building block lipid II and prev...
Source: Journal of Molecular Biology - June 5, 2019 Category: Molecular Biology Source Type: research

A MICOS–TIM22 Association Promotes Carrier Import into Human Mitochondria
Publication date: Available online 17 May 2019Source: Journal of Molecular BiologyAuthor(s): Sylvie Callegari, Tobias Müller, Christian Schulz, Christof Lenz, Daniel C. Jans, Mirjam Wissel, Felipe Opazo, Silvio O. Rizzoli, Stefan Jakobs, Henning Urlaub, Peter Rehling, Markus DeckersAbstractMitochondrial membrane proteins with internal targeting signals are inserted into the inner membrane by the carrier translocase (TIM22 complex). For this, precursors have to be initially directed from the TOM complex in the outer mitochondrial membrane across the intermembrane space toward the TIM22 complex. How these two translocat...
Source: Journal of Molecular Biology - June 5, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 31 May 2019Source: Journal of Molecular Biology, Volume 431, Issue 12Author(s): (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - June 3, 2019 Category: Molecular Biology Source Type: research

Human Telomere Repeat Binding Factor TRF1 Replaces TRF2 Bound to Shelterin Core Hub TIN2 when TPP1 Is Absent
Publication date: Available online 31 May 2019Source: Journal of Molecular BiologyAuthor(s): Tomáš Janovič, Martin Stojaspal, Pavel Veverka, Denisa Horáková, Ctirad HofrAbstractHuman telomeric repeat binding factors TRF1, TRF2 along with TIN2 form the core of the shelterin complex that protects chromosome ends against unwanted end-joining and DNA repair. We applied a single-molecule approach to assess TRF1-TIN2-TRF2 complex formation in solution at physiological conditions. Fluorescence Cross-Correlation Spectroscopy (FCCS) was used to describe the complex assembly by analyzing how coincident f...
Source: Journal of Molecular Biology - June 2, 2019 Category: Molecular Biology Source Type: research

Identification of an Alternating-Access Dynamics Mutant of EmrE with Impaired Transport
Publication date: Available online 31 May 2019Source: Journal of Molecular BiologyAuthor(s): Chao Wu, Samantha A. Wynne, Nathan E. Thomas, Eva-Maria Uhlemann, Christopher G. Tate, Katherine A. Henzler-WildmanAbstractProteins that perform active transport must alternate the access of a binding site, first to one side of a membrane and then to the other, resulting in the transport of bound substrates across the membrane. To better understand this process, we sought to identify mutants of the small multidrug resistance transporter EmrE with reduced rates of alternating access. We performed extensive scanning mutagenesis by ch...
Source: Journal of Molecular Biology - June 2, 2019 Category: Molecular Biology Source Type: research

RGS6 and RGS7 Discriminate between the Highly-Similar Gαi and Gαo Proteins Using a Two-Tiered Specificity Strategy
Publication date: Available online 30 May 2019Source: Journal of Molecular BiologyAuthor(s): Ran Israeli, Ali Asli, Meirav Avital-Shacham, Mickey KosloffAbstractRGS6 and RGS7 are Regulators of G protein Signaling (RGS) proteins that inactivate heterotrimeric (αβγ) G proteins and mediate diverse biological functions, such as cardiac and neuronal signaling. Uniquely, both RGS6 and RGS7 can discriminate between Gαo and Gαi1 – two similar Gα subunits that belong to the same Gi sub-family. Here, we show that the isolated RGS domains of RGS6 and RGS7 are sufficient to achieve this specifi...
Source: Journal of Molecular Biology - May 31, 2019 Category: Molecular Biology Source Type: research

The mechanisms of substrate selection, catalysis and translocation by the elongating RNA polymerase
Publication date: Available online 31 May 2019Source: Journal of Molecular BiologyAuthor(s): Georgiy A. Belogurov, Irina ArtsimovitchAbstractMulti-subunit DNA-dependent RNA polymerases synthesize all classes of cellular RNAs, ranging from short regulatory transcripts to gigantic messenger RNAs. RNA polymerase has to make each RNA product in just one try, even if it takes millions of successive nucleotide addition steps. During each step, RNAP selects a correct substrate, adds it to a growing chain, and moves one nucleotide forward before repeating the cycle. Yet RNA synthesis is anything but monotonous: RNA polymerase freq...
Source: Journal of Molecular Biology - May 31, 2019 Category: Molecular Biology Source Type: research

Tol Energy-Driven Localization of pal and Anchoring to the Peptidoglycan Promote Outer Membrane Constriction
Publication date: Available online 31 May 2019Source: Journal of Molecular BiologyAuthor(s): Mélissa Petiti, Bastien Serrano, Laura Faure, Roland Lloubes, Tâm Mignot, Denis DucheAbstractDuring cell division, Gram-negative bacteria must coordinate inner membrane (IM) invagination, peptidoglycan (PG) synthesis and cleavage and outer membrane (OM) constriction. The OM constriction remains largely enigmatic and the nature of this process, passive or active, is under debate. The proton-motive force (PMF) dependent Tol-Pal system performs a network of interactions within these three compartments. Here we confirm tha...
Source: Journal of Molecular Biology - May 31, 2019 Category: Molecular Biology Source Type: research

Transcription of Bacterial Chromatin
Publication date: Available online 31 May 2019Source: Journal of Molecular BiologyAuthor(s): Beth A. Shen, Robert LandickAbstractDecades of research have probed the interplay between chromatin (genomic DNA associated with proteins and RNAs) and transcription by RNA polymerase (RNAP) in all domains of life. In bacteria, chromatin is compacted into a membrane-free region known as the nucleoid that changes shape and composition depending on the bacterial state. Transcription plays a key role in both shaping the nucleoid and organizing it into domains. At the same time, chromatin impacts transcription by at least five distinct...
Source: Journal of Molecular Biology - May 31, 2019 Category: Molecular Biology Source Type: research

Regulation of Survival Networks in Senescent Cells: From Mechanisms to Interventions
Publication date: Available online 31 May 2019Source: Journal of Molecular BiologyAuthor(s): Abel Soto-Gamez, Wim J. Quax, Marco DemariaAbstractCellular senescence is a state of stable cell cycle arrest arising in response to DNA and mitochondrial damages. Senescent cells undergo morphological, structural and functional changes which are influenced by a number of variables, including time, stress, tissue, and cell type. The heterogeneity of the senescent phenotype is exemplified by the many biological properties that senescent cells can cover. The advent of innovative model organisms has demonstrated a functional role of s...
Source: Journal of Molecular Biology - May 31, 2019 Category: Molecular Biology Source Type: research

Computational Resources for Molecular Biology
Publication date: Available online 30 May 2019Source: Journal of Molecular BiologyAuthor(s): Boris Lenhard, Michael J.E. Sternberg (Source: Journal of Molecular Biology)
Source: Journal of Molecular Biology - May 30, 2019 Category: Molecular Biology Source Type: research

Autophagy Exacerbates Muscle Wasting in Cancer Cachexia and Impairs Mitochondrial Function
Publication date: Available online 28 May 2019Source: Journal of Molecular BiologyAuthor(s): Fabio Penna, Riccardo Ballarò, Paula Martinez-Cristobal, David Sala, David Sebastian, Silvia Busquets, Maurizio Muscaritoli, Josep M. Argilés, Paola Costelli, Antonio ZorzanoAbstractCancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss and muscle wasting that impairs patients' quality of life and survival. Aim of this work was to evaluate the impact of either autophagy inhibition (knocking-down beclin-1) or promotion (overexpressing TP53INP2/DOR) on cancer-induced muscle wasting. In C26 t...
Source: Journal of Molecular Biology - May 30, 2019 Category: Molecular Biology Source Type: research

Engineering Strategy and Vector Library for the Rapid generation of Modular Light-Controlled Protein–Protein Interactions
Publication date: Available online 29 May 2019Source: Journal of Molecular BiologyAuthor(s): Alexandra-Madelaine Tichy, Elliot J. Gerrard, Julien M.D. Legrand, Robin M. Hobbs, Harald JanovjakAbstractOptogenetics enables the spatio-temporally precise control of cell and animal behaviour. Many optogenetic tools are driven by light-controlled protein–protein-interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying light-controlled PPIs to new target proteins is challenging because it is difficult to predict which of the many available LSDs, if any, will yield robust light regulation....
Source: Journal of Molecular Biology - May 30, 2019 Category: Molecular Biology Source Type: research

Establishing Pure Cancer Organoid Cultures: Identification, Selection and Verification of Cancer Phenotypes and Genotypes
Publication date: Available online 29 May 2019Source: Journal of Molecular BiologyAuthor(s): Nina Wallaschek, Carolin Niklas, Malvika Pompaiah, Armin Wiegering, Christoph-Thomas Germer, Stefan Kircher, Stefanie Brändlein, Katja Maurus, Andreas Rosenwald, Helen H.N. Yan, Suet Y. Leung, Sina BartfeldAbstractPrecision medicine requires in vitro models which will both faithfully recapitulate the features of an individual's disease and enable drug testing on a wide variety of samples covering the greatest range of phenotypes possible for a particular disease. Organoid technology has immense potential to fulfill this demand...
Source: Journal of Molecular Biology - May 30, 2019 Category: Molecular Biology Source Type: research