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Journal of Molecular Biology

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https://www.readbyqxmd.com/read/28088481/saxs-structural-studies-of-dps-from-deinococcus-radiodurans-highlights-the-conformation-of-the-mobile-n-terminal-extensions
#1
Sandra P Santos, Maxime G Cuypers, Adam Round, Stephanie Finet, Theyencheri Narayanan, Edward P Mitchell, Célia V Romão
The radiation resistant bacterium Deinococcus radiodurans contains two DNA binding proteins from starved cells (Dps): Dps1 (DR2263) and Dps2 (DRB0092). These are suggested to play a role in DNA interaction, manganese and iron storage. The proteins assemble as a conserved dodecameric structure with structurally uncharacterized N-terminal extensions. In the case of DrDps1 these extensions have been proposed to be involved in DNA interactions, while in DrDps2 their function has yet to be established. The reported data reveals the relative position of the N-terminal extensions to the dodecameric sphere in solution for both Dps...
January 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28088480/sensing-membrane-curvature-in-macroautophagy
#2
REVIEW
Nathan Nguyen, Vladimir Shteyn, Thomas J Melia
In response to intracellular stress events ranging from starvation to pathogen invasion, the cell activates one or more forms of macroautophagy. The key event in these related pathways is the de novo formation of a new organelle called the autophagosome, which surrounds and sequesters either random portions of the cytoplasm or selectively targets individual intracellular challenges. Thus the autophagosome is a flexible membrane platform with dimensions that ultimately depend upon the target cargo. The intermediate membrane, termed the phagophore or isolation membrane, is a cup-like structure with a clear concave face and a highly curved rim...
January 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28088479/three-dimensional-structure-of-full-length-ntrx-an-unusual-member-of-the-ntrc-family-of-response-regulators
#3
Ignacio Fernández, Irina Cornaciu, Mariela Del Carmen Carrica, Emiko Uchikawa, Guillaume Hoffmann, Rodrigo Sieira, José Antonio Márquez, Fernando A Goldbaum
Bacteria sense and adapt to environmental changes using two-component systems (TCS). These signaling pathways are formed by a histidine kinase (HK) that phosphorylates a response regulator (RR), which finally modulates the transcription of target genes. The bacterium Brucella abortus codes for a TCS formed by the HK NtrY and the RR NtrX that participates in sensing low oxygen tension and in generating an adaptive response. NtrX is a modular protein with REC, AAA+ and DNA binding domains, an architecture that classifies it among the NtrC subfamily of RRs...
January 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28087262/molecular-mechanisms-of-autophagy-part-b
#4
EDITORIAL
Sharon A Tooze, James H Hurley
No abstract text is available yet for this article.
January 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28082080/bacteriophage-spp1-pac-cleavage-a-precise-cut-without-sequence-specificity-requirement
#5
Karima Djacem, Paulo Tavares, Leonor Oliveira
In many tailed bacteriophages DNA packaging is initiated by recognition and cleavage of a specific sequence pac, by the small (TerS) and large (TerL) terminase subunits. It was previously shown that the SPP1 pac region has two sequences where TerS binds (pacR and pacL) flanking the segment where TerL cleaves the SPP1 DNA (pacC). However, the pac specific sequences required to achieve this endonucleolytic cut were not established. Their characterization is essential to understand the underlying mechanism. We show that the pacR sequence localized within 35bp downstream of the pac cut can be extensively degenerated, including its c1 and c2 repeats, and that only disruption of a 5bp polyadenine tract impairs pac cleavage...
January 9, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28077293/autophagosome-maturation-and-fusion
#6
REVIEW
Fulvio Reggiori, Christian Ungermann
Macroautophagy or simply autophagy, is a degradative pathway that delivers cytoplasmic components, including cytosol and organelles, to the lysosome in double-membrane vesicles called autophagosomes. This process is initiated at the pre-autophagosomal structure or phagophore assembly site (PAS), and involves a number of highly conserved autophagy-related (Atg) proteins. Those support the generation and conversion of an open membranous cistern known as the phagophore or isolation membrane, into a closed autophagosome...
January 8, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28077285/a-fluorophore-fusion-construct-of-human-profilin-i-with-non-compromized-poly-l-proline-binding-capacity-suitable-for-imaging
#7
Michaela Nejedla, Zhilun Li, Anna E Masser, Matteo Biancospino, Matthias Spiess, Sebastian D Mackowiak, Marc R Friedländer, Roger Karlsson
Profilin is vital for actin organization in eukaryotic cells. It controls actin filament formation by binding monomeric actin and numerous proteins involved in polarized actin assembly. Important for the latter is the interaction surface formed by the N- and C-terminal helices, which pack close to each other on one side of the molecule at distance from the actin site and mediate binding to poly-proline sequences present in many of the targeted proteins. Via these interactions profilin contributes to the spatiotemporal control of actin filament growth...
January 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28077284/structural-biology-of-the-cvt-pathway
#8
REVIEW
Akinori Yamasaki, Nobuo N Noda
Macroautophagy is a degradation process in which autophagosomes are generated to isolate and transport various materials, including damaged organelles and protein aggregates, as cargos to the lysosomes or vacuoles. Bulk autophagy is one of the two types of macroautophagy, which is triggered by starvation and targets non-specific cargos. The second type, i.e., selective autophagy, identifies and preferentially degrades specific cargos via receptor recognition. Cytoplasm-to-vacuole targeting (Cvt) is a selective autophagy pathway that specifically transports vacuolar hydrolases into the vacuole in budding yeast cells and has been extensively studied as a model of selective autophagy...
January 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28069372/rna-exosome-and-non-coding-rna-coupled-mechanisms-in-aid-mediated-genomic-alterations
#9
REVIEW
Brice Laffleur, Uttiya Basu, Junghyun Lim
The eukaryotic RNA exosome is a well-conserved protein complex with ribonuclease activity implicated in RNA metabolism. Various families of non-coding RNAs have been identified as substrates of the complex, underscoring its role as a non-coding RNA processing/degradation unit. However, the role of RNA exosome and its RNA processing activity on DNA mutagenesis/alteration events have not been investigated until recently. B lymphocytes use two DNA alteration mechanisms, class switch recombination (CSR) and somatic hypermutation (SHM), to re-engineer their antibody gene expressing loci until a tailored antibody gene for a specific antigen is satisfactorily generated...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28065739/r-loop-depletion-by-over-expressed-rnase-h1-in-mouse-b-cells-increases-activation-induced-deaminase-access-to-the-transcribed-strand-without-altering-frequency-of-isotype-switching
#10
Robert W Maul, Hyongi Chon, Kiran Sakhuja, Susana M Cerritelli, Lina A Gugliotti, Patricia J Gearhart, Robert J Crouch
R-loops, three-strand structures consisting of mRNA hybridized to the complementary DNA and a single-stranded DNA loop, are formed in switch regions on the heavy-chain immunoglobulin locus. To determine if R-loops have a direct effect on any of the steps involved in isotype switching, we generated a transgenic mouse that over-expressed RNase H1, an enzyme that cleaves the RNA of RNA/DNA hybrids in B cells. R-loops in the switch μ region were depleted by 70% in ex vivo activated splenic B cells. Frequencies of isotype switching to IgG1, IgG2b, IgG2c, and IgG3 were the same as C57BL/6 control cells...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28065740/bacterial-signaling-to-the-nervous-system-via-toxins-and-metabolites
#11
REVIEW
Nicole J Yang, Isaac M Chiu
Mammalian hosts interface intimately with commensal and pathogenic bacteria. It is increasingly clear that molecular interactions between the nervous system and microbes contribute to health and disease. Both commensal and pathogenic bacteria are capable of producing molecules that act on neurons and affect essential aspects of host physiology. Here we highlight several classes of physiologically important molecular interactions that occur between bacteria and the nervous system. First, clostridial neurotoxins block neurotransmission to or from neurons by targeting the SNARE complex, causing the characteristic paralyses of botulism and tetanus during bacterial infection...
January 5, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28043854/compound-selectivity-and-target-residence-time-of-kinase-inhibitors-studied-with-surface-plasmon-resonance
#12
Nicole Willemsen-Seegers, Joost C M Uitdehaag, Martine B W Prinsen, Judith R F de Vetter, Jos de Man, Masaaki Sawa, Yusuke Kawase, Rogier C Buijsman, Guido J R Zaman
Target residence time (τ) has been suggested to be a better predictor of the biological activity of kinase inhibitors than inhibitory potency (IC50) in enzyme assays. Surface plasmon resonance binding assays for 46 human protein and lipid kinases were developed. The association and dissociation constants of 80 kinase inhibitor interactions were determined. τ and equilibrium affinity constants (KD) were calculated to determine kinetic selectivity. Comparison of τ and KD or IC50 values revealed a strikingly different view on the selectivity of several kinase inhibitors, including the multi-kinase inhibitor ponatinib, which was tested on 10 different kinases...
December 30, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28025039/computation-resources-for-molecular-biology-special-issue-2017
#13
EDITORIAL
Marina I Ostankovitch, Michael J E Sternberg
No abstract text is available yet for this article.
December 23, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28013031/functional-and-molecular-insights-of-hydrogen-sulfide-signaling-and-protein-sulfhydration
#14
REVIEW
Nilkantha Sen
Hydrogen sulfide (H2S) a novel gasotransmitter is endogenously synthesized by multiple enzymes that are differentially expressed in the peripheral tissues and central nervous systems. H2S regulates a wide range of physiological processes ranging from cardiovascular, neuronal, immune, respiratory, gastrointestinal, liver, and endocrine systems by influencing cellular signaling pathways and sulfhydration of target proteins. This review focuses on the recent progress made in H2S signaling that affects mechanistic and functional aspects of several biological processes such as autophagy, inflammation, proliferation and differentiation of stem cell, cell survival/death, and cellular metabolism under both physiological and pathological conditions...
December 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28013030/interaction-of-e-coli-hsp90-with-dnak-involves-the-dnaj-binding-region-of-dnak
#15
Andrea N Kravats, Shannon M Doyle, Joel R Hoskins, Olivier Genest, Erin Doody, Sue Wickner
The 90-kDa heat shock protein (Hsp90) is a widely conserved and ubiquitous molecular chaperone that participates in ATP-dependent protein remodeling in both eukaryotes and prokaryotes. It functions in conjunction with Hsp70 and the Hsp70 cochaperones, an Hsp40 (J-protein) and a nucleotide exchange factor. In Escherichia coli, the functional collaboration between Hsp90Ec and Hsp70, DnaK, requires that the two chaperones directly interact. We used molecular docking to model the interaction of Hsp90Ec and DnaK...
December 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28013029/charting-developmental-dissolution-of-pluripotency
#16
REVIEW
Joerg Betschinger
The formation of tissues and organs during metazoan development begs fundamental questions of cellular plasticity: How can the very same genome program have diverse cell types? How do cell identity programs unfold during development in space and time? How can defects in these mechanisms cause disease and also provide opportunities for therapeutic intervention? And ultimately, can developmental programs be exploited for bioengineering tissues and organs? Understanding principle designs of cellular identity and developmental progression is crucial for providing answers...
December 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28013028/h3k4-methyltransferase-activity-is-required-for-mll4-protein-stability
#17
Younghoon Jang, Chaochen Wang, Lenan Zhuang, Chengyu Liu, Kai Ge
Transcriptional enhancers play a key role in cell type-specific gene expression and cell fate transition. Enhancers are marked by histone H3K4 mono- and di-methylation (H3K4me1/2). The tumor suppressor MLL4 (KMT2D) is a major enhancer H3K4 mono- and di-methyltransferase with a partial functional redundancy with MLL3 (KMT2C). However, the functional role of MLL4 enzymatic activity remains elusive. To address this issue, we have generated MLL4 enzyme-dead knock-in (KI) embryonic stem (ES) cells and mice, which carry Y5477A/Y5523A/Y5563A mutations in the enzymatic SET domain of the MLL4 protein...
December 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27988225/the-epigenetic-paradox-of-pluripotent-es-cells
#18
REVIEW
Nicola Festuccia, Inma Gonzalez, Pablo Navarro
The propagation and maintenance of gene expression programs are at the foundation of the preservation of cell identity. A large and complex set of epigenetic mechanisms enables the long-term stability and inheritance of transcription states. A key property of authentic epigenetic regulation is being independent from the instructive signals used for its establishment. This makes epigenetic regulation, particularly epigenetic silencing, extremely robust and powerful to lock regulatory states and stabilise cell identity...
December 15, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27986571/the-journey-of-the-autophagosome-through-mammalian-cell-organelles-and-membranes
#19
REVIEW
Diana Molino, Naïma Zemirli, Patrice Codogno, Etienne Morel
Autophagy is an intracellular degradation process carried out by a double-membrane organelle, termed the autophagosome, which sequesters cytoplasmic material destined for lysosomal degradation and recycling. Autophagy and autophagosome biogenesis are highly conserved processes in eukaryotes and are essential for cell survival, stress responses, and homeostasis. Autophagosomes are dynamic and complex organelles that can originate from several different membrane compartments. Autophagosomes traffic through the cell to fuse with lysosomes or other compartments...
December 13, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27986570/the-c-box-region-of-maf1-regulates-transcriptional-activity-and-protein-stability
#20
Ajay Pradhan, Amy M Hammerquist, Akshat Khanna, Sean P Curran
MAF1 is a conserved negative regulator of RNA polymerase (pol) III and intracellular lipid homeostasis across species. Here, we show that the MAF1 C-box region negatively regulates its activity. Mutations in Caenorhabditis elegans mafr-1 that truncate the C-box retain the ability to inhibit the transcription of RNA pol III targets, reduce lipid biogenesis, and lower reproductive output. In human cells, C-box deletion of MAF1 leads to increased MAF1 nuclear localization and enhanced repression of ACC1 and FASN, but with impaired repression of RNA pol III targets...
December 13, 2016: Journal of Molecular Biology
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