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Journal of Molecular Biology

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https://www.readbyqxmd.com/read/30021116/formation-of-a-secretion-competent-protein-complex-by-a-dynamic-wrap-around-binding-mechanism
#1
Arun A Gupta, Ines Reinartz, Gogulan Karunanithy, Alessandro Spilotros, Venkateswara Rao Jonna, Anders Hofer, Dmitri I Svergun, Andrew J Baldwin, Alexander Schug, Magnus Wolf-Watz
Bacterial virulence is typically initiated by translocation of effector or toxic proteins across host cell membranes. A class of Gram-negative pathogenic bacteria including Yersinia pseudotuberculosis and Yersinia pestis accomplishes this objective with a protein assembly called the Type III secretion system (T3SS). Yersinia effector proteins (Yop) are presented to the translocation apparatus through formation of specific complexes with their cognate chaperones (Syc). In the complexes where the structure is available, the Yops are extended and wrap around their cognate chaperone...
July 15, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30009770/modifying-chromatin-by-histone-tail-clipping
#2
REVIEW
Gajendra Kumar Azad, Swati Swagatika, Manoj Kumawat, Ramesh Kumawat, Raghuvir Singh Tomar
Post-translational modifications (PTMs) of histone proteins play a crucial role in the regulation of chromatin structure and functions. Studies in the last few decades have revealed the significance of histone PTMs in key cellular processes including DNA replication, repair, transcription, apoptosis and cell cycle regulation. The PTMs on histones are carried out by chromatin modifiers which are reversible in nature. The dynamic activity of chromatin modifiers maintains the levels of different PTMs on histones...
July 13, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30017921/amyloid-by-design-intrinsic-regulation-of-microbial-amyloid-assembly
#3
REVIEW
Maya Deshmukh, Margery L Evans, Matthew R Chapman
The term amyloid has historically been used to describe fibrillar aggregates formed as the result of protein misfolding and that are associated with a range of diseases broadly termed amyloidoses. The discovery of 'functional amyloids' expanded the amyloid umbrella to encompass aggregates structurally similar to disease-associated amyloids but that engage in a variety of biologically useful tasks without incurring toxicity. The mechanisms by which functional amyloid systems ensure nontoxic assembly has provided insights into potential therapeutic strategies for treating amyloidoses...
July 12, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30017920/structural-and-functional-characterization-of-the-bcsg-subunit-of-the-cellulose-synthase-in-salmonella-typhimurium
#4
Lei Sun, Peter Vella, Robert Schnell, Anna Polyakova, Gleb Bourenkov, Fengyang Li, Annika Cimdins, Thomas R Schneider, Ylva Lindqvist, Michael Y Galperin, Gunter Schneider, Ute Römling
Many bacteria secrete cellulose, which forms the structural basis for bacterial multicellular aggregates, termed biofilms. The cellulose synthase complex of Salmonella typhimurium consists of the catalytic subunits BcsA and BcsB and several auxiliary subunits that are encoded by two divergently transcribed operons, bcsRQABZC and bcsEFG. Expression of the bcsEFG operon is required for full-scale cellulose production but the functions of its products are not fully understood. This work aimed to characterize the BcsG subunit of the cellulose synthase, which consists of an N-terminal transmembrane fragment and a C-terminal domain in the periplasm...
July 12, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30017919/multilayer-view-of-pathogenic-snvs-in-human-interactome-through-in-silico-edgetic-profiling
#5
Hongzhu Cui, Nan Zhao, Dmitry Korkin
Non-synonymous mutations linked to the complex diseases often have a global impact on a biological system, affecting large biomolecular networks and pathways. However, the magnitude of the mutation-driven effects on the macromolecular network is yet to be fully explored. In this work, we present an systematic multi-level characterization of human mutations associated with genetic disorders by determining their individual and combined interaction-rewiring, "edgetic", effects on the human interactome...
July 12, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30017918/methods-for-physical-characterization-of-phase-separated-bodies-and-membrane-less-organelles
#6
REVIEW
Diana M Mitrea, Bappaditya Chandra, Mylene C Ferrolino, Eric B Gibbs, Michele Tolbert, Michael R White, Richard W Kriwacki
Biochemical processes within eukaryotic cells are partially controlled through spatial and temporal organization of macromolecules. Cellular compartmentalization has long been appreciated, starting with early microscopic observations of unicellular organisms, and animal and plant tissues in the late 1600s, and later refined in the early 1950s through the advent of electron microscopy and improved sample preparation methods [1]. Two classes of sub-cellular compartments organize biological macromolecules within an eukaryotic cell...
July 12, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30017917/aggregation-phase-separation-and-spatial-morphologies-of-the-assemblies-of-fg-nucleoporins
#7
REVIEW
Anton Zilman
Nuclear Pore Complex (NPC) is a biomolecular "nanomachine" that controls nucleocytoplasmic transport in eukaryotic cells. The key component of the functional architecture of the NPC is the assembly of intrinsically disordered proteins that line its passageway and play a central role in the NPC transport mechanism. Due to paucity of experimental methods capable to directly probe the morphology of this assembly in intact NPCs, much of our knowledge about its properties derives from in vitro experiments augmented by theoretical and computational modeling...
July 12, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30009771/the-role-of-functional-amyloids-in-bacterial-virulence
#8
REVIEW
Nani Van Gerven, Sander E Van der Verren, Dirk M Reiter, Han Remaut
Amyloid fibrils are best known as a product of human and animal protein misfolding disorders, where amyloid formation is associated with cytotoxicity and disease. It is now evident that for some proteins, the amyloid state constitutes the native structure and serves a functional role. These functional amyloids are proving widespread in bacteria and fungi, fulfilling diverse functions as structural components in biofilms or spore coats, as toxins and surface-active fibers, as epigenetic material, peptide reservoirs or adhesins mediating binding to and internalization into host cells...
July 12, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30009769/perspectives-on-structural-molecular-biology-visualization-from-past-to-present
#9
REVIEW
Arthur J Olson
Visualization has been a key technology in the progress of structural molecular biology for as long as the field has existed. This perspective describes the nature of the visualization process in structural studies, how it has evolved over the years, and its relationship to the changes in technology that have supported and driven it. It focuses on how technical advances have changed the way we look at and interact with molecular structure, and how structural biology has fostered and challenged that technology...
July 12, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30006266/de-novo-designed-alpha-sheet-peptides-inhibit-functional-amyloid-formation-of-streptococcus-mutans-biofilms
#10
Natasha Paranjapye, Valerie Daggett
Streptococcus mutans is a bacterial species that predominates in the oral microbiome. S. mutans binds to the tooth surface, metabolizes sugars and produces acid, leading to cavity formation. S. mutans can also cause infectious endocarditis. Recent evidence suggests that S. mutans biofilms contain amyloid fibrils. Amyloids are insoluble fibrillar protein aggregates, and bacteria use functional amyloids to improve robustness of their biofilms. While the functional amyloids in bacteria such as E. coli and S. aureus have been heavily investigated, little is known about the mechanism of S...
July 10, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30006265/how-mitochondrial-metabolism-contributes-to-macrophage-phenotype-and-functions
#11
REVIEW
Khaddouj Benmoussa, Johan Garaude, Rebeca Acín-Pérez
Metabolic reprogramming of cells from the innate immune system is one of the most noteworthy topics in immunological research nowadays. Upon infection or tissue damage innate immune cells, such as macrophages, mobilize various immune and metabolic signals to mount a response best suited to eradicate the threat. Current data indicate that both the immune and metabolic responses are closely interconnected. On account of its peculiar position in regulating both of these processes, the mitochondrion has emerged as a critical organelle that orchestrates the coordinated metabolic and immune adaptations in macrophages...
July 10, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30003887/enabling-precision-medicine-through-integrative-network-models
#12
REVIEW
Victoria Yao, Aaron K Wong, Olga G Troyanskaya
A key challenge in precision medicine lies in understanding molecular-level underpinnings of complex human disease. Biological networks in multicellular organisms can generate hypotheses about disease genes, pathways, and their behavior in disease-related tissues. Diverse functional genomic data, including expression, protein-protein interaction, and relevant sequence and literature information can be utilized to build integrative networks that provide both genome-wide coverage as well as contextual specificity and accuracy...
July 9, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29990470/mechanisms-of-gasdermin-family-members-in-inflammasome-signaling-and-cell-death
#13
REVIEW
Shouya Feng, Daniel Fox, Si Ming Man
The Gasdermin (GSDM) family consists of Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME) and Pejvakin (PJVK). GSDMD is activated by inflammasome-associated inflammatory caspases. Cleavage of GSDMD by human or mouse caspase-1, human caspase-4, human caspase-5, and mouse caspase-11, liberates the N-terminal effector domain from the C-terminal inhibitory domain. The N-terminal domain oligomerizes in the cell membrane and forms a pore of 10-16 nm in diameter, through which substrates of a smaller diameter, such as interleukin (IL)-1β and IL-18, are secreted...
July 7, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29990469/direct-detection-of-membrane-inserting-fragments-defines-the-translocation-pores-of-a-family-of-pathogenic-toxins
#14
Kathleen E Orrell, Åsa Tellgren-Roth, Mercedes Di Bernardo, Zhifen Zhang, Flavia Cuviello, Jasmin Lundqvist, Gunnar von Heijne, IngMarie Nilsson, Roman A Melnyk
Large Clostridial Toxins (LCTs) are a family of homologous proteins toxins that are directly responsible for the symptoms associated with a number of Clostridial infections that cause disease in humans and in other animals. LCTs damage tissues by delivering a glucosyltransferase domain, which inactivates small GTPases, across the endosomal membrane and into the cytosol of target cells. Elucidating the mechanism of translocation for LCTs has been hampered by difficulties associated with identifying marginally hydrophobic segments that insert into the bounding membrane to form the translocation pore...
July 7, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29981746/folding-up-and-moving-on-nascent-protein-folding-on-the-ribosome
#15
REVIEW
Christian M Kaiser, Kaixian Liu
All cellular proteins are synthesized by the ribosome, an intricate molecular machine that translates the information of protein coding genes into the amino acid alphabet. The linear polypeptides synthesized by the ribosome must generally fold into specific three-dimensional structures to become biologically active. Folding has long been recognized to begin before synthesis is complete. Recently, biochemical and biophysical studies have shed light onto how the ribosome shapes the folding pathways of nascent proteins...
July 5, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29981745/cancer-associated-2-oxoglutarate-analogues-modify-histone-methylation-by-inhibiting-histone-lysine-demethylases
#16
Tuomas Laukka, Matti Myllykoski, Ryan E Looper, Peppi Koivunen
Histone lysine demethylases (KDMs) are 2-oxoglutarate-dependent dioxygenases (2-OGDDs) that regulate gene expression by altering chromatin structure. Their dysregulation has been associated with many cancers. We set out to study the catalytic and inhibitory properties of human KDM4A, KDM4B, KDM5B, KDM6A and KDM6B, aiming in particular to reveal which of these enzymes are targeted by cancer-associated 2-oxoglutarate (2-OG) analogues. We used affinity-purified insect cell-produced enzymes and synthetic peptides with trimethylated lysines as substrates for the in vitro enzyme activity assays...
July 5, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29969581/terminal-regions-confer-plasticity-to-the-tetrameric-assembly-of-human-hspb2-and-hspb3
#17
Alice R Clark, Wilma Vree Egberts, Frances D L Kondrat, Gillian R Hilton, Nicholas J Ray, Ambrose R Cole, John A Carver, Justin L P Benesch, Nicholas H Keep, Wilbert C Boelens, Christine Slingsby
Heterogeneity in small heat shock proteins (sHsps) spans multiple spatiotemporal regimes - from fast fluctuations of part of the protein, to conformational variability of tertiary structure, plasticity of the interfaces, and polydispersity of the inter-converting, and co-assembling oligomers. This heterogeneity and dynamic nature of sHsps has significantly hindered their structural characterisation. Atomic-coordinates are particularly lacking for vertebrate sHsps, where most available structures are of extensively truncated homomers...
June 30, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29966609/the-arabidopsis-histone-chaperone-fact-role-of-the-hmg-box-domain-of-ssrp1
#18
Alexander Pfab, Jesper T Grønlund, Philipp Holzinger, Gernot Längst, Klaus D Grasser
Histone chaperones play critical roles in regulated structural transitions of chromatin in eukaryotic cells that involve nucleosome disassembly and reassembly. The histone chaperone FACT is a heterodimeric complex consisting in plants and metazoa of SSRP1/SPT16 and is involved in dynamic nucleosome reorganisation during various DNA-dependent processes including transcription, replication and repair. The C-terminal HMG-box domain of the SSRP1 subunit mediates interactions with DNA and nucleosomes in vitro, but its relevance in vivo is unclear...
June 29, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29966608/drug-response-prediction-by-globally-capturing-drug-and-cell-line-information-in-a-heterogeneous-network
#19
Duc-Hau Le, Van-Huy Pham
One of the most important problem in personalized medicine research is to precisely predict the drug response for each patient. Due to relationships between drugs, recent machine learning-based methods have solved this problem using multi-task learning models. However, chemical relationships between drugs have not been considered. In addition, using very high dimensions of -omics data (e.g., genetic variant and gene expression) also limits the prediction power. A recent dual-layer network-based method was proposed to overcome these limitations by embedding gene expression features into a cell line similarity network, and drug relationships in a chemical structure-based drug similarity network...
June 29, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29964047/protein-engineering-reveals-mechanisms-of-functional-amyloid-formation-in-pseudomonas-aeruginosa-biofilms
#20
Alissa Bleem, Gunna Christiansen, Daniel J Madsen, Hans Maric, Kristian Strømgaard, James D Bryers, Valerie Daggett, Rikke L Meyer, Daniel E Otzen
Amyloids are typically associated with neurodegenerative diseases, but recent research demonstrates that several bacteria utilize functional amyloid fibrils to fortify the biofilm extracellular matrix and thereby resist antibiotic treatments. In Pseudomonas aeruginosa, these fibrils are composed predominantly of FapC, a protein with high sequence conservation among the genera. Previous studies established FapC as the major amyloid subunit, but its mechanism of fibril formation in P. aeruginosa remained largely unexplored...
June 29, 2018: Journal of Molecular Biology
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