31,283 results match your criteria Journal of Molecular Biology[Journal]


Structural Basis for the Distinct Membrane Binding Activity of the Homologous C2A Domains of Myoferlin and Dysferlin.

J Mol Biol 2019 Apr 17. Epub 2019 Apr 17.

Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, Texas, United States; Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX, United States. Electronic address:

Dysferlin has been implicated in acute membrane repair processes, whereas myoferlin's activity is maximal during the myoblast fusion stage of early skeletal muscle cell development. Both proteins are similar in size and domain structure; however, despite the overall similarity, myoferlin's known physiological functions do not overlap with those of dysferlin. Here we present for the first time the X-ray crystal structure of human myoferlin C2A to 1. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.04.006DOI Listing

Variations in Core Packing of GP2 from Old World Mammarenaviruses in their Post-Fusion Conformations Affect Membrane-Fusion Efficiencies.

J Mol Biol 2019 Apr 17. Epub 2019 Apr 17.

Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address:

Lassa virus (LASV) is a notorious human pathogen in West Africa. Its class-I trimeric spike complex displays a distinct architecture, and its cell entry mechanism involves unique attributes not shared by other related viruses. We determined the crystal structure of the GP2 fusion glycoprotein from the spike complex of LASV (GP2) in its post-fusion conformation. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00222836193020
Publisher Site
http://dx.doi.org/10.1016/j.jmb.2019.04.012DOI Listing
April 2019
1 Read

Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection.

J Mol Biol 2019 Apr 16. Epub 2019 Apr 16.

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, United States of America; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, United States of America; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, United States of America. Electronic address:

Urinary tract infections (UTIs) are the most commonly reported infections in adult women and have high rates of recurrence, especially in postmenopausal women. Recurrent UTI (RUTI) greatly reduces quality of life, places a significant burden on the healthcare system, and contributes to antimicrobial resistance. Because treatment of RUTI by long-term antibiotic therapy is often ineffective or poorly tolerated in elderly women, new therapies must be developed. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00222836193020
Publisher Site
http://dx.doi.org/10.1016/j.jmb.2019.04.008DOI Listing
April 2019
1 Read

Bacterial Transcription Factors: Regulation by Pick 'N' Mix.

J Mol Biol 2019 Apr 15. Epub 2019 Apr 15.

Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK. Electronic address:

Transcription in most bacteria is tightly regulated in order to facilitate bacterial adaptation to different environments, and transcription factors play a key role in this. Here we give a brief overview of the essential features of bacterial transcription factors and how they affect transcript initiation at target promoters. We focus on complex promoters that are regulated by combinations of activators and repressors, combinations of repressors only, or combinations of activators. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.04.011DOI Listing
April 2019
1 Read

Deciphering the Nucleotide and RNA Binding Selectivity of the Mayaro Virus Macro Domain.

J Mol Biol 2019 Apr 15. Epub 2019 Apr 15.

Department of Pharmacy, University of Patras, GR-26504, Patras, Greece. Electronic address:

Mayaro virus (MAYV) is a member of Togaviridae family which also includes Chikungunya virus as a notorious member. MAYV recently emerged in urban areas of the Americas, and this emergence emphasized the current paucity of knowledge about its replication cycle. The macro domain (MD) of MAYV belongs to the N-terminal region of its non-structural protein 3, part of the replication complex. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.04.013DOI Listing

Crystal Structure and Directed Evolution of Specificity of NlaIV Restriction Endonuclease.

J Mol Biol 2019 Apr 14. Epub 2019 Apr 14.

International Institute of Molecular and Cell Biology, Trojdena 4, 02-109 Warsaw, Poland. Electronic address:

Specificity engineering is challenging, and particularly difficult for enzymes that have the catalytic machinery and specificity determinants in close proximity. Restriction endonucleases have been used as a paradigm for protein engineering, but successful cases are rare. Here, we present the results of a directed evolution approach to the engineering of a dimeric, blunt end cutting restriction enzyme NlaIV (GGN/NCC). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.04.010DOI Listing

Can Predicted Protein 3D-Structures Provide Reliable Insights into whether Missense Variants Are Disease-Associated?

J Mol Biol 2019 Apr 14. Epub 2019 Apr 14.

Structural Bioinformatics Group, Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Sir Ernst Chain Building, Imperial College London, London SW7 2AZ, UK. Electronic address:

Knowledge of protein structure can be used to predict the phenotypic consequence of a missense variant. Since structural coverage of the human proteome can be roughly tripled to over 50% of the residues if homology-predicted structures are included in addition to experimentally-determined coordinates, it is important to assess the reliability of using predicted models when analysing missense variants. Accordingly, we assess whether a missense variant is structurally damaging by using experimental and predicted structures. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.04.009DOI Listing

Location, Location, Location-Commensalism, Damage and Evolution of the Pathogenic Neisseria.

Authors:
H Steven Seifert

J Mol Biol 2019 Apr 12. Epub 2019 Apr 12.

Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address:

The 10 human-restricted Neisseria species all colonize mucosal surfaces, but show a spectrum of pathogenicity. The commensal Neisseria do not normally cause pathology, while the two pathogenic species, Neisseria meningitidis and Neisseria gonorrhoeae, straddle the border between commensalism and pathogenicity. Why the pathogenic Neisseria continue to mediate host damage after thousands of years of co-evolution with their human host, and why the commensal species have not acquired the ability to damage the host, if this capability provides a selective advantage, is not understood. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00222836193018
Publisher Site
http://dx.doi.org/10.1016/j.jmb.2019.04.007DOI Listing
April 2019
3 Reads

Corrigendum to "Coordinated Transcriptional Regulation of Hspa1a Gene by Multiple Transcription Factors: Crucial Roles for HSF-1, NF-Y, NF-κB, and CREB" [J. Mol. Biol. (2014) 426, 116-135].

J Mol Biol 2019 Apr 11. Epub 2019 Apr 11.

Cardiovascular Genetics Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, India. Electronic address:

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00222836193015
Publisher Site
http://dx.doi.org/10.1016/j.jmb.2019.03.026DOI Listing
April 2019
1 Read

Mechanisms of Bacterial Transcription Termination.

J Mol Biol 2019 Apr 9. Epub 2019 Apr 9.

Department of Molecular Biology and Genetics, Biotechnology Building, Cornell University, Ithaca, NY 14853. Electronic address:

Bacterial transcription termination, described mostly for E. coli, occurs in three recognized ways: intrinsic termination, an activity only of the core RNAP enzyme and transcript sequences that encode an RNA hairpin and terminal uridine-rich segment; termination by the enzyme Rho, an ATP-dependent RNA translocase that releases RNA by forcing uncharacterized structural changes in the elongating complex; and Mfd-dependent termination, the activity of an ATP-dependent DNA translocase that is thought to dissociate the elongation complex by exerting torque on a stalled RNAP. Intrinsic termination can be described in terms of the nucleic acid movements in the process, whereas the enzymatic mechanisms have been illuminated importantly by definitive structural and biochemical analysis of their activity. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.04.003DOI Listing

Allosteric Regulation of Cyclin-B Binding by the Charge State of Catalytic Lysine in CDK1 Is Essential for Cell Cycle Progression.

J Mol Biol 2019 Apr 8. Epub 2019 Apr 8.

Department of Biological Sciences, Tata Institute of Fundamental Research (TIFR), Mumbai, 400005, India. Electronic address:

Cyclin dependent kinase 1 (CDK1) is essential for cell cycle progression. While dependence of CDK activity on cyclin levels is well established, molecular mechanisms that regulate their binding are less understood. Here, we report for the first time that CDK1:cyclin-B binding is not default but rather determined by the evolutionarily conserved catalytic residue, lysine-33 in CDK1. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.04.005DOI Listing
April 2019
4.333 Impact Factor

Phenotypic Heterogeneity Generated by Histidine Kinase-Based Signaling Networks.

J Mol Biol 2019 Apr 7. Epub 2019 Apr 7.

Munich Center for Integrated Protein Science (CiPSM) at the Department of Microbiology, Ludwig-Maximilians-Universität München, 82152 Martinsried, Germany.

A complex relationship exists between environmental factors, signaling networks and phenotypic individuality in bacteria. In this review, we will focus on the organization, function and control points of multiple-input histidine kinase-based signaling cascades as a source of phenotypic heterogeneity. In particular, we will examine the quorum sensing cascade in Vibrio harveyi and the pyruvate sensor network in Escherichia coli. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.032DOI Listing
April 2019
2 Reads

Breaching the Barrier: Quantifying Antibiotic Permeability across Gram-Negative Bacterial Membranes.

J Mol Biol 2019 Apr 5. Epub 2019 Apr 5.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, D-28759, Bremen, Germany. Electronic address:

The double membrane cell envelope of Gram negative bacteria is a sophisticated barrier that facilitates the uptake of nutrients and protects the organism from toxic compounds. An antibiotic molecule must find its way through the negatively charged lipopolysaccharide layer on the outer surface, pass through either a porin or the hydrophobic layer of the outer membrane, then traverse the hydrophilic peptidoglycan layer only to find another hydrophobic lipid bilayer before it finally enters the cytoplasm, where it typically finds its target. This complex uptake pathway with very different physico-chemical properties is one reason that Gram-negatives are intrinsically protected against multiple classes of antibiotic-like molecules, and is likely the main reason that in vitro target based screening programmes have failed to deliver novel antibiotics for these organisms. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.031DOI Listing

Adenomatous Polyposis Coli as a Scaffold for Microtubule End-Binding Proteins.

J Mol Biol 2019 Apr 6. Epub 2019 Apr 6.

Grenoble Institut des Neurosciences, INSERM U1216, Univ. Grenoble Alpes, Grenoble, 38000 France. Electronic address:

End-binding proteins (EBs), referred to as the core components of the microtubule plus-end tracking protein network, interact with the C-terminus of the adenomatous polyposis coli (APC) tumor suppressor. This interaction is disrupted in colon cancers expressing truncated APC. APC and EBs act in synergy to regulate microtubule dynamics during spindle formation, chromosome segregation and cell migration. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00222836193017
Publisher Site
http://dx.doi.org/10.1016/j.jmb.2019.03.028DOI Listing
April 2019
4 Reads

β-Lactamases and β-Lactamase Inhibitors in the 21 Century.

J Mol Biol 2019 Apr 5. Epub 2019 Apr 5.

School of Cellular and Molecular Medicine, University of Bristol Biomedical Sciences Building, University Walk, Bristol BS8 1TD, United Kingdom. Electronic address:

The β-lactams retain a central place in the antibacterial armamentarium. In Gram-negative bacteria β-lactamase enzymes that hydrolyse the amide bond of the four-membered β-lactam ring are the primary resistance mechanism, with multiple enzymes disseminating on mobile genetic elements across opportunistic pathogens such as Enterobacteriaceae (e.g. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00222836193018
Publisher Site
http://dx.doi.org/10.1016/j.jmb.2019.04.002DOI Listing
April 2019
6 Reads

Cryo-EM Analysis Reveals Structural Basis of Helicobacter pylori VacA Toxin Oligomerization.

J Mol Biol 2019 Apr 4. Epub 2019 Apr 4.

Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Helicobacter pylori colonizes the human stomach and contributes to the development of gastric cancer and peptic ulcer disease. H. pylori secretes a pore-forming toxin called vacuolating cytotoxin A (VacA), which contains two domains (p33 and p55) and assembles into oligomeric structures. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.029DOI Listing
April 2019
2 Reads

Role of Phenol-Soluble Modulins in Staphylococcus epidermidis Biofilm Formation and Infection of Indwelling Medical Devices.

J Mol Biol 2019 Apr 5. Epub 2019 Apr 5.

Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health, 50 South Drive, Bethesda, MD 20814, USA. Electronic address:

Phenol-soluble modulins (PSMs) are amphipathic, alpha-helical peptides that are secreted by staphylococci in high amounts in a quorum-sensing-controlled fashion. Studies performed predominantly in Staphylococcus aureus showed that PSMs structure biofilms, which results in reduced biofilm mass, while it has also been reported that S. aureus PSMs stabilize biofilms due to amyloid formation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.030DOI Listing
April 2019
1 Read

Menacing Mold: Recent Advances in Aspergillus Pathogenesis and Host Defense.

J Mol Biol 2019 Apr 4. Epub 2019 Apr 4.

Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Infectious Disease Service, Department of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. Electronic address:

The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans inhale several hundred to several thousand Aspergillus conidia (i. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.027DOI Listing
April 2019
2 Reads

A c-di-GMP-Based Switch Controls Local Heterogeneity of Extracellular Matrix Synthesis which Is Crucial for Integrity and Morphogenesis of Escherichia coli Macrocolony Biofilms.

J Mol Biol 2019 Apr 4. Epub 2019 Apr 4.

Institut für Biologie/Mikrobiologie, Humboldt-Universität zu Berlin, 10115 Berlin, Germany. Electronic address:

The extracellular matrix in macrocolony biofilms of Escherichia coli is arranged in a complex large-scale architecture, with homogenic matrix production close to the surface, whereas zones further below display pronounced local heterogeneity of matrix production, which results in distinct three-dimensional architectural structures. Combining genetics, cryosectioning and fluorescence microscopy of macrocolony biofilms, we demonstrate here in situ that this local matrix heterogeneity is generated by a c-di-GMP-dependent molecular switch characterized by several nested positive and negative feedback loops. In this switch, the trigger phosphodiesterase PdeR is the key component for establishing local heterogeneity in the activation of the transcription factor MlrA, which in turn activates expression of the major matrix regulator CsgD. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.04.001DOI Listing

Dementia, Brain Disorders and Molecular Mechanisms.

J Mol Biol 2019 Apr 28;431(9):1709-1710. Epub 2019 Mar 28.

Milteny Biotech GmbH, Friedrich-Ebert-Str.68, 51429, Bergisch Gladbach, Germany. Electronic address:

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.025DOI Listing

Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking.

J Mol Biol 2019 Mar 28. Epub 2019 Mar 28.

Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address:

MET, the product of the c-MET proto-oncogene, and its ligand hepatocyte growth factor/scatter factor (HGF/SF) control survival, proliferation and migration during development and tissue regeneration. HGF/SF-MET signaling is equally crucial for growth and metastasis of a variety of human tumors, but resistance to small-molecule inhibitors of MET kinase develops rapidly and therapeutic antibody targeting remains challenging. We made use of the designed ankyrin repeat protein (DARPin) technology to develop an alternative approach for inhibiting MET. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.024DOI Listing
March 2019
1 Read

Glucose-6-Phosphate Dehydrogenase from the Human Pathogen Trypanosoma cruzi Evolved Unique Structural Features to Support Efficient Product Formation.

J Mol Biol 2019 Mar 28. Epub 2019 Mar 28.

Laboratory Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Mataojo 2020, 11400-, Montevideo, Uruguay. Electronic address:

Glucose-6-phosphate dehydrogenase (G6PDH) is the key enzyme supplying reducing power (NADPH) to the cells, by oxidation of glucose-6-phosphate (G6P), and in the process providing a precursor of ribose-5-phosphate. G6PDH is also a virulence factor of pathogenic trypanosomatid parasites. To uncover the biochemical and structural features that distinguish TcG6PDH from its human homolog, we have now solved the crystal structures of the G6PDH from Trypanosoma cruzi (TcG6PDH), alone and in complex with G6P. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00222836183069
Publisher Site
http://dx.doi.org/10.1016/j.jmb.2019.03.023DOI Listing
March 2019
3 Reads

Stability and Inter-domain Interactions Modulate Amyloid Binding Activity of a General Amyloid Interaction Motif.

J Mol Biol 2019 Mar 28. Epub 2019 Mar 28.

The M13 tip protein, g3p, binds the C-terminal domain of the bacterial membrane protein TolA via β-sheet augmentation, facilitating viral entry into Escherichia coli. G3p binding leads to rearrangement of the β strands and partial unfolding of TolA. G3p also binds multiple amyloid assemblies with high affinity, and it can remodel them into amorphous aggregates. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.022DOI Listing
March 2019
1 Read

Potent Neutralization of Staphylococcal Enterotoxin B In Vivo by Antibodies that Block Binding to the T-Cell Receptor.

J Mol Biol 2019 Mar 27. Epub 2019 Mar 27.

Banting and Best Department of Medical Research, Department of Molecular Genetics, and the Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Electronic address:

To develop an antibody (Ab) therapeutic against staphylococcal enterotoxin B (SEB), a potential incapacitating bioterrorism agent and a major cause of food poisoning, we developed a "class T" anti-SEB neutralizing Ab (GC132) targeting an epitope on SEB distinct from that of previously developed "class M" Abs. A systematic engineering approach was applied to affinity-mature Ab GC132 to yield an optimized therapeutic candidate (GC132a) with sub-nanomolar binding affinity. Mapping of the binding interface by hydrogen-deuterium exchange coupled to mass spectrometry revealed that the class T epitope on SEB overlapped with the T-cell receptor binding site, whereas other evidence suggested that the class M epitope overlapped with the binding site for the major histocompatibility complex. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.017DOI Listing
March 2019
5 Reads

Pervasive Pairwise Intragenic Epistasis among Sequential Mutations in TEM-1 β-Lactamase.

J Mol Biol 2019 Mar 25. Epub 2019 Mar 25.

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA. Electronic address:

Interactions between mutations play a central role in shaping the fitness landscape, but a clear picture of intragenic epistasis has yet to emerge. To further reveal the prevalence and patterns of intragenic epistasis, we present a survey of epistatic interactions between sequential mutations in TEM-1 β-lactamase. We measured the fitness effect of ~12,000 pairs of consecutive amino acid substitutions and used our previous study of the fitness effects of single amino acid substitutions to calculate epistasis for over 8000 mutation pairs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.020DOI Listing
March 2019
1 Read

Clarifying the Link between Toxin-Antitoxin Modules and Bacterial Persistence.

J Mol Biol 2019 Mar 23. Epub 2019 Mar 23.

Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, United Kingdom. Electronic address:

While most of a bacterial population is killed upon antibiotic exposure, a fraction transiently exhibits a multidrug-tolerant phenotype termed antibiotic persistence. This phenomenon enables the bacteria to escape killing by drugs and is presumed to be, at least partly, responsible for the recalcitrance of many bacterial infections. For this reason, understanding mechanisms allowing a fraction of a bacterial population to become transiently multidrug-tolerant represents an essential step to eradicate these persisting subpopulations. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.019DOI Listing

Dropping Out and Other Fates of Transmembrane Segments Inserted by the SecA ATPase.

J Mol Biol 2019 Mar 23. Epub 2019 Mar 23.

Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697-4560, USA. Electronic address:

Type II single-span membrane proteins, such as CadC or RodZ, lacking a signal sequence and having a far-downstream hydrophobic segment, require the SecA secretion motor for insertion into the inner membrane of Escherichia coli. Using two chimeric single-span proteins containing a designed hydrophobic segment H, we have determined the requirements for SecA-mediated secretion, the molecular distinction between TM domains and signal peptides, and the propensity for hydrophobic H-segments to remain embedded within the bilayer after targeting. By means of engineered H-segments and a strategically placed SPase I cleavage site, we determined how targeting and stability of the chimeric proteins are affected by the length and hydrophobicity of the H-segment. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.021DOI Listing

The Many Facets of the Small Non-coding RNA RsaE (RoxS) in Metabolic Niche Adaptation of Gram-Positive Bacteria.

J Mol Biol 2019 Mar 23. Epub 2019 Mar 23.

Institute of Molecular Infection Biology, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany. Electronic address:

Small regulatory RNAs (sRNAs) are increasingly recognized as players in the complex regulatory networks governing bacterial gene expression. RsaE (synonym RoxS) is an sRNA that is highly conserved in bacteria of the Bacillales order. Recent analyses in Bacillus subtilis, Staphylococcus aureus and Staphylococcus epidermidis identified RsaE/RoxS as a potent riboregulator of central carbon metabolism and energy balance with many molecular RsaE/RoxS functions and targets being shared across species. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.016DOI Listing

RNA Sequence Features Are at the Core of Influenza A Virus Genome Packaging.

J Mol Biol 2019 Mar 23. Epub 2019 Mar 23.

Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology and Microbial Pathogenesis, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA. Electronic address:

The influenza A virus (IAV), a respiratory pathogen for humans, poses serious medical and economic challenges to global healthcare systems. The IAV genome, consisting of eight single-stranded viral RNA segments, is incorporated into virions by a complex process known as genome packaging. Specific RNA sequences within the viral RNA segments serve as signals that are necessary for genome packaging. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.018DOI Listing

Dissection of Protonation Sites for Antibacterial Recognition and Transport in QacA, a Multi-Drug Efflux Transporter.

J Mol Biol 2019 Mar 22. Epub 2019 Mar 22.

Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India, 560012. Electronic address:

QacA is a drug:H antiporter (DHA) with 14 transmembrane helices, that confers antibacterial resistance to methicillin-resistant Staphylococcus aureus (MRSA) strains, with homologs in other pathogenic organisms. It is a highly promiscuous antiporter, capable of H- driven efflux of a wide array of cationic antibacterial compounds and dyes. Our study, using a homology model of QacA, reveals a group of six protonatable residues in its vestibule. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.015DOI Listing
March 2019
1 Read

Respiration Enhances TDP-43 Toxicity, but TDP-43 Retains Some Toxicity in the Absence of Respiration.

J Mol Biol 2019 Mar 21. Epub 2019 Mar 21.

Department of Pharmacology, University of Nevada, Reno, NV, USA. Electronic address:

The trans-activating response DNA-binding protein 43 (TDP-43) is a transcriptional repressor and splicing factor. TDP-43 is normally mostly in the nucleus, although it shuttles to the cytoplasm. Mutations in TDP-43 are one cause of familial amyotrophic lateral sclerosis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.014DOI Listing
March 2019
1 Read

Dynamics of Replication Fork Progression Following Helicase-Polymerase Uncoupling in Eukaryotes.

J Mol Biol 2019 Mar 17. Epub 2019 Mar 17.

Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. Electronic address:

Leading-strand polymerase stalling at DNA damage impairs replication fork progression. Using biochemical approaches, we show this arises due to both slower template unwinding following helicase-polymerase uncoupling and establishment of prolonged stalled fork structures. Fork slowing and stalling occur at structurally distinct lesions, are always associated with continued lagging-strand synthesis, are observed when either Pol ε or Pol δ stalls at leading-strand damage, and do not require specific helicase-polymerase coupling factors. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00222836193013
Publisher Site
http://dx.doi.org/10.1016/j.jmb.2019.03.011DOI Listing
March 2019
7 Reads

Phylogenetic Analysis with Improved Parameters Reveals Conservation in lncRNA Structures.

J Mol Biol 2019 Apr 16;431(8):1592-1603. Epub 2019 Mar 16.

Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA. Electronic address:

The existence of evolutionary conservation in base pairing is strong evidence for functional elements of RNA structure, although available tools for rigorous identification of structural conservation are limited. R-scape is a recently developed program for statistical prediction of pairwise covariation from sequence alignments, but it initially showed limited utility on long RNAs, especially those of eukaryotic origin. Here we show that R-scape can be adapted for a more powerful analysis of structure conservation in long RNA molecules, including mammalian lncRNAs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.012DOI Listing

ISG15: It's Complicated.

J Mol Biol 2019 Mar 16. Epub 2019 Mar 16.

Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA. Electronic address:

Interferon-stimulated gene product 15 (ISG15) is a key component of host responses to microbial infection. Despite having been known for four decades, grasping the functions and features of ISG15 has been a slow and elusive process. Substantial work over the past two decades has greatly enhanced this understanding, revealing the complex and variable nature of this protein. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.013DOI Listing
March 2019
2 Reads

G-Quadruplexes in Human Ribosomal RNA.

J Mol Biol 2019 Mar 15. Epub 2019 Mar 15.

Center for the Origin of Life, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA. Electronic address:

rRNA is the single most abundant polymer in most cells. Mammalian rRNAs are nearly twice as large as those of prokaryotes. Differences in rRNA size are due to expansion segments, which contain extended tentacles in metazoans. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.010DOI Listing
March 2019
1 Read

Microglia-Specific Metabolic Changes in Neurodegeneration.

Authors:
Blanca I Aldana

J Mol Biol 2019 Apr 13;431(9):1830-1842. Epub 2019 Mar 13.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address:

The high energetic demand of the brain deems this organ rather sensitive to changes in energy supply. Therefore, even minor alterations in energy metabolism may underlie detrimental disturbances in brain function, contributing to the generation and progression of neurodegenerative diseases. Considerable evidence supports the key role of deficits in cerebral energy metabolism, particularly hypometabolism of glucose and mitochondrial dysfunction, in the pathophysiology of brain disorders. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.006DOI Listing

The Balancing Act of Intrinsically Disordered Proteins: Enabling Functional Diversity while Minimizing Promiscuity.

J Mol Biol 2019 Apr 13;431(8):1650-1670. Epub 2019 Mar 13.

VIB-VUB Center for Structural Biology, Vlaams Instituut voor Biotechnologie, Pleinlaan 2, 1050 Brussels, Belgium. Electronic address:

Intrinsically disordered proteins (IDPs) or regions (IDRs) perform diverse cellular functions, but are also prone to forming promiscuous and potentially deleterious interactions. We investigate the extent to which the properties of, and content in, IDRs have adapted to enable functional diversity while limiting interference from promiscuous interactions in the crowded cellular environment. Information on protein sequences, their predicted intrinsic disorder, and 3D structure contents is related to data on protein cellular concentrations, gene co-expression, and protein-protein interactions in the well-studied yeast Saccharomyces cerevisiae. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453724PMC
April 2019
3 Reads

A High-Resolution Luminescent Assay for Rapid and Continuous Monitoring of Protein Translocation across Biological Membranes.

J Mol Biol 2019 Apr 13;431(8):1689-1699. Epub 2019 Mar 13.

School of Biochemistry, University of Bristol, Bristol, UK; BrisSynBio, University of Bristol, Bristol, UK. Electronic address:

Protein translocation is a fundamental process in biology. Major gaps in our understanding of this process arise due the poor sensitivity, low time resolution and irreproducibility of translocation assays. To address this, we applied NanoLuc split-luciferase to produce a new strategy for measuring protein transport. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461198PMC

Roles of the Hydrophobic Gate and Exit Channel in Vigna radiata Pyrophosphatase Ion Translocation.

J Mol Biol 2019 Apr 13;431(8):1619-1632. Epub 2019 Mar 13.

Department of Life Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan. Electronic address:

Membrane-embedded pyrophosphatase (M-PPase) hydrolyzes pyrophosphate to drive ion (H and/or Na) translocation. We determined crystal structures and functions of Vigna radiata M-PPase (VrH-PPase), the VrH-PPase-2P complex and mutants at hydrophobic gate (residue L555) and exit channel (residues T228 and E225). Ion pore diameters along the translocation pathway of three VrH-PPases complexes (P-, 2P- and imidodiphosphate-bound states) present a unique wave-like profile, with different pore diameters at the hydrophobic gate and exit channel, indicating that the ligands induced pore size alterations. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.009DOI Listing
April 2019
2 Reads

Lactate-Mediated Protection of Retinal Ganglion Cells.

J Mol Biol 2019 Apr 13;431(9):1878-1888. Epub 2019 Mar 13.

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Department of Ophthalmology, Rigshospitalet-Glostrup, Glostrup, Denmark. Electronic address:

Loss of retinal ganglion cells (RGCs) is a leading cause of blinding conditions. The purpose of this study was to evaluate the effect of extracellular l-lactate on RGC survival facilitated through lactate metabolism and ATP production. We identified lactate as a preferred energy substrate over glucose in murine RGCs and showed that lactate metabolism and consequently increased ATP production are crucial components in promoting RGC survival during energetic crisis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.005DOI Listing

Expanded CUG Repeats Trigger Disease Phenotype and Expression Changes through the RNAi Machinery in C. elegans.

J Mol Biol 2019 Apr 14;431(9):1711-1728. Epub 2019 Mar 14.

Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel. Electronic address:

Myotonic dystrophy type 1 is an autosomal-dominant inherited disorder caused by the expansion of CTG repeats in the 3' untranslated region of the DMPK gene. The RNAs bearing these expanded repeats have a range of toxic effects. Here we provide evidence from a Caenorhabditis elegans myotonic dystrophy type 1 model that the RNA interference (RNAi) machinery plays a key role in causing RNA toxicity and disease phenotypes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.003DOI Listing
April 2019
1 Read

rRNA and tRNA Bridges to Neuronal Homeostasis in Health and Disease.

J Mol Biol 2019 Apr 12;431(9):1763-1779. Epub 2019 Mar 12.

Institute of Applied Physiology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany; Institute of Anatomy and Cell Biology, Medical Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany. Electronic address:

Dysregulation of protein translation is emerging as a unifying mechanism in the pathogenesis of many neuronal disorders. Ribosomal RNA (rRNA) and transfer RNA (tRNA) are structural molecules that have complementary and coordinated functions in protein synthesis. Defects in both rRNAs and tRNAs have been described in mammalian brain development, neurological syndromes, and neurodegeneration. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.004DOI Listing

Structural Explorations of NCp7-Nucleic Acid Complexes Give Keys to Decipher the Binding Process.

J Mol Biol 2019 Mar 12. Epub 2019 Mar 12.

LBPA, UMR 8113, ENS Paris-Saclay-CNRS, 61 avenue du Président Wilson, 94235 Cachan cedex, France. Electronic address:

A comprehensive view of all the structural aspects related to NCp7 is essential to understand how this protein, crucial in many steps of the HIV-1 cycle, binds and anneals nucleic acids (NAs), mainly thanks to two zinc fingers, ZF1 and ZF2. Here, we inspected the structural properties of the available experimental models of NCp7 bound to either DNA or RNA molecules, or free of ligand. Our analyses included the characterization of the relative positioning of ZF1 and ZF2, accessibility measurements and the exhaustive, quantitative mapping of the contacts between amino acids and nucleotides by a recent tessellation method, VLDM. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.002DOI Listing
March 2019
3 Reads

NapA (Rv0430), a Novel Nucleoid-Associated Protein that Regulates a Virulence Operon in Mycobacterium tuberculosis in a Supercoiling-Dependent Manner.

J Mol Biol 2019 Apr 12;431(8):1576-1591. Epub 2019 Mar 12.

Department of Microbiology and Cell Biology, Indian Institute of Science, C.V. Raman Avenue, Bangalore 560012, India; Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India. Electronic address:

Comparison of Mycobacterium tuberculosis with Escherichia coli reveals a reduction in the diversity of DNA-managing proteins, such as DNA topoisomerases, although genome sizes are similar for the two species. The same is true for nucleoid-associated proteins (NAPs), important factors in bacterial chromosome compaction, chromosome remodeling, and regulation of gene expression. In a search for still uncharacterized NAPs, we found that M. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.02.029DOI Listing
April 2019
1 Read

RNA Splicing: A New Paradigm in Host-Pathogen Interactions.

J Mol Biol 2019 Apr 8;431(8):1565-1575. Epub 2019 Mar 8.

Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India. Electronic address:

RNA splicing brings diversity to the eukaryotic proteome. Different spliced variants of a gene may differ in their structure, function, localization, and stability influencing protein stoichiometry and physiological outcomes. Alternate spliced variants of different genes are known to associate with various chronic pathologies including cancer. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.03.001DOI Listing
April 2019
4.333 Impact Factor

Influence of Cholesterol and Its Stereoisomers on Members of the Serotonin Receptor Family.

J Mol Biol 2019 Apr 8;431(8):1633-1649. Epub 2019 Mar 8.

Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK; Department of Chemistry, University of Oxford, Oxford, OX1 3TA, Oxford, UK. Electronic address:

Despite the ubiquity of cholesterol within the cell membrane, the mechanism by which it influences embedded proteins remains elusive. Numerous G-protein coupled receptors exhibit dramatic responses to membrane cholesterol with regard to the ligand-binding affinity and functional properties, including the 5-HT receptor family. Here, we use over 25 μs of unbiased atomistic molecular dynamics simulations to identify cholesterol interaction sites in the 5-HT and 5-HT receptors and evaluate their impact on receptor structure. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.02.030DOI Listing

GUILDify v2.0: A Tool to Identify Molecular Networks Underlying Human Diseases, Their Comorbidities and Their Druggable Targets.

J Mol Biol 2019 Mar 7. Epub 2019 Mar 7.

Integrative Biomedical Informatics Group, Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Catalonia 08003, Spain; Department of Pharmacology and Personalised Medicine, CARIM, FHML, Maastricht University, Universiteitssingel 50, 6229, ER, Maastricht, the Netherlands. Electronic address:

The genetic basis of complex diseases involves alterations on multiple genes. Unraveling the interplay between these genetic factors is key to the discovery of new biomarkers and treatments. In 2014, we introduced GUILDify, a web server that searches for genes associated to diseases, finds novel disease genes applying various network-based prioritization algorithms and proposes candidate drugs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.02.027DOI Listing
March 2019
1 Read

EvoDesign: Designing Protein-Protein Binding Interactions Using Evolutionary Interface Profiles in Conjunction with an Optimized Physical Energy Function.

J Mol Biol 2019 Mar 7. Epub 2019 Mar 7.

Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

EvoDesign (https://zhanglab.ccmb.med. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.02.028DOI Listing
March 2019
1 Read

Comparison of RNA Editing Activity of APOBEC1-A1CF and APOBEC1-RBM47 Complexes Reconstituted in HEK293T Cells.

J Mol Biol 2019 Mar 4;431(7):1506-1517. Epub 2019 Mar 4.

Molecular and Computational Biology, Department of Biological Sciences, Chemistry, University of Southern California, Los Angeles, CA 90089, USA; Genetic, Molecular and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Center of Excellence in NanoBiophysics, University of Southern California, Los Angeles, CA 90089, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA. Electronic address:

RNA editing is an important form of regulating gene expression and activity. APOBEC1 cytosine deaminase was initially characterized as pairing with a cofactor, A1CF, to form an active RNA editing complex that specifically targets APOB RNA in regulating lipid metabolism. Recent studies revealed that APOBEC1 may be involved in editing other potential RNA targets in a tissue-specific manner, and another protein, RBM47, appears to instead be the main cofactor of APOBEC1 for editing APOB RNA. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.02.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443457PMC

Visualizing Biological Membrane Organization and Dynamics.

Authors:
Marc Baaden

J Mol Biol 2019 Mar 4. Epub 2019 Mar 4.

Laboratoire de Biochimie Théorique, CNRS, UPR9080, Univ Paris Diderot, Sorbonne Paris Cité, PSL Research University, 13 rue Pierre et Marie Curie, 75005 Paris, France. Electronic address:

Biological membranes are fascinating. Santiago Ramón y Cajal, who received the Nobel prize in 1906 together with Camillo Golgi for their work on the nervous system, wrote "[…]in the study of this membrane[…] I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life". The visualization and conceptualization of these biological objects have profoundly shaped many aspects of modern biology, drawing inspiration from experiments, computer simulations, and the imagination of scientists and artists. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.02.018DOI Listing