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https://www.readbyqxmd.com/read/28813412/the-primed-snare-complexin-synaptotagmin-complex-for-neuronal-exocytosis
#1
Qiangjun Zhou, Peng Zhou, Austin L Wang, Dick Wu, Minglei Zhao, Thomas C Südhof, Axel T Brunger
Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE-complexin-synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28808690/the-hemagglutinin-esterase-fusion-glycoprotein-is-a-primary-determinant-of-the-exceptional-thermal-and-acid-stability-of-influenza-d-virus
#2
Jieshi Yu, Busha Hika, Runxia Liu, Zizhang Sheng, Ben M Hause, Feng Li, Dan Wang
Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiments demonstrated that only IDV had a high residual infectivity (~2.5 log units of 50% tissue culture infective dose [TCID50]/ml) after a 60-min exposure to 53°C in solution at a neutral pH, and remarkably, IDV retained this infectivity even after exposure to 53°C for 120 min...
July 2017: MSphere
https://www.readbyqxmd.com/read/28808054/mst4-phosphorylates-acap4-to-orchestrate-apical-membrane-remodeling-during-gastric-acid-secretion
#3
Xiao Yuan, Phil Y Yao, Jiying Jiang, Yin Zhang, Zeqi Su, Wendy Yao, Xueying Wang, Ping Gui, McKay Mullen, Calmour Henry, Tarsha Ward, Wenwen Wang, Larry Brako, Ruijun Tian, Xuannv Zhao, Fengsong Wang, Xinwang Cao, Dongmei Wang, Xing Liu, Xia Ding, Xuebiao Yao
The digestion in the stomach depends on acidification of the lumen. Histamine-elicited acid secretion is triggered by activation of PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. Our recent study revealed the functional role of PKA-MST4-ezrin signaling axis in histamine-elicited acid secretion (Jiang et al., 2015. J. Biol. Chem. 290, 28272-28285). However, it remains uncharacterized how PKA-MST4-ezrin signaling axis operates the insertion of H,K-ATPases into the apical plasma membranes of gastric parietal cells...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28808010/voltage-gated-calcium-flux-mediates-escherichia-coli-mechanosensation
#4
Giancarlo N Bruni, R Andrew Weekley, Benjamin J T Dodd, Joel M Kralj
Electrically excitable cells harness voltage-coupled calcium influx to transmit intracellular signals, typically studied in neurons and cardiomyocytes. Despite intense study in higher organisms, investigations of voltage and calcium signaling in bacteria have lagged due to their small size and a lack of sensitive tools. Only recently were bacteria shown to modulate their membrane potential on the timescale of seconds, and little is known about the downstream effects from this modulation. In this paper, we report on the effects of electrophysiology in individual bacteria...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807998/immunogenicity-and-structures-of-a-rationally-designed-prefusion-mers-cov-spike-antigen
#5
Jesper Pallesen, Nianshuang Wang, Kizzmekia S Corbett, Daniel Wrapp, Robert N Kirchdoerfer, Hannah L Turner, Christopher A Cottrell, Michelle M Becker, Lingshu Wang, Wei Shi, Wing-Pui Kong, Erica L Andres, Arminja N Kettenbach, Mark R Denison, James D Chappell, Barney S Graham, Andrew B Ward, Jason S McLellan
Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807884/escrt-and-autophagies-endosomal-functions-and-beyond
#6
REVIEW
Christophe Lefebvre, Renaud Legouis, Emmanuel Culetto
ESCRT (endosomal sorting complex required for transport) machinery has been initially identified for its role during endocytosis, which allows membrane proteins and lipids to be degraded in the lysosome. ESCRT function is required to form intraluminal vesicles permitting internalization of cytosolic components or membrane embedded cargoes and promoting endosome maturation. ESCRT machinery also contributes to multiple key cell mechanisms in which it reshapes membranes. In addition, ESCRT actively participates in different types of autophagy processes for degrading cytosolic components, such as endosomal microautophagy and macroautophagy...
August 11, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28807829/the-magnaporthe-oryzae-alt-a-1-like-protein-mohrip1-binds-to-the-plant-plasma-membrane
#7
Yi Zhang, Yingbo Liang, Yijie Dong, Yuhan Gao, Xiufen Yang, Jingjing Yuan, Dewen Qiu
MoHrip1, a protein isolated from Magnaporthe oryzae, belongs to the Alt A 1 (AA1) family. mohrip1 mRNA levels showed inducible expression throughout the infection process in rice. To determine the location of MoHrip1 in M. oryzae, a mohrip1-gfp mutant was generated. Fluorescence microscopy observations and western blotting analysis showed that MoHrip1 was both present in the secretome and abundant in the fungal cell wall. To obtain MoHrip1 protein, we carried out high-yield expression of MoHrip1 in Pichia pastoris...
August 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28807151/exocytotic-fusion-pores-as-a-target-for-therapy
#8
REVIEW
Jernej Jorgačevski, Marko Kreft, Robert Zorec
Regulated exocytosis can be split into a sequence of steps ending with the formation and the dilation of a fusion pore, a neck-like connection between the vesicle and the plasma membrane. Each of these steps is precisely controlled to achieve the optimal spatial and temporal profile of the release of signalling molecules. At the level of the fusion pore, tuning of the exocytosis can be achieved by preventing its formation, by stabilizing the unproductive narrow fusion pore, by altering the speed of fusion pore expansion and by completely closing the fusion pore...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28806415/synthetic-mrna-is-a-more-reliable-tool-for-the-delivery-of-dna-targeting-proteins-into-the-cell-nucleus-than-fusion-with-a-protein-transduction-domain
#9
Ivan Leontovyc, David Habart, Sarka Loukotova, Lucie Kosinova, Jan Kriz, Frantisek Saudek, Tomas Koblas
Cell reprogramming requires efficient delivery of reprogramming transcription factors into the cell nucleus. Here, we compared the robustness and workload of two protein delivery methods that avoid the risk of genomic integration. The first method is based on fusion of the protein of interest to a protein transduction domain (PTD) for delivery across the membranes of target cells. The second method relies on de novo synthesis of the protein of interest inside the target cells utilizing synthetic mRNA (syn-mRNA) as a template...
2017: PloS One
https://www.readbyqxmd.com/read/28806263/18f-dcfbc-prostate-specific-membrane-antigen-targeted-pet-ct-imaging-in-localized-prostate-cancer-correlation-with-multiparametric-mri-and-histopathology
#10
Baris Turkbey, Esther Mena, Liza Lindenberg, Stephen Adler, Sandra Bednarova, Rose Berman, Anita T Ton, Yolanda McKinney, Philip Eclarinal, Craig Hill, George Afari, Sibaprasad Bhattacharyya, Ronnie C Mease, Maria J Merino, Paula M Jacobs, Bradford J Wood, Peter A Pinto, Martin G Pomper, Peter L Choyke
PURPOSE: To assess the ability of (N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-F-fluorobenzyl-L-cysteine) (F-DCFBC), a prostate-specific membrane antigen-targeted PET agent, to detect localized prostate cancer lesions in correlation with multiparametric MRI (mpMRI) and histopathology. METHODS: This Health Insurance Portability and Accountability Act of 1996-compliant, prospective, institutional review board-approved study included 13 evaluable patients with localized prostate cancer (median age, 62...
August 12, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28803692/a-janus-faced-im30-ring-involved-in-thylakoid-membrane-fusion-is-assembled-from-im30-tetramers
#11
Michael Saur, Raoul Hennig, Phoebe Young, Kristiane Rusitzka, Nadja Hellmann, Jennifer Heidrich, Nina Morgner, Jürgen Markl, Dirk Schneider
Biogenesis and dynamics of thylakoid membranes likely involves membrane fusion events. Membrane attachment of the inner membrane-associated protein of 30 kDa (IM30) affects the structure of the lipid bilayer, finally resulting in membrane fusion. Yet, how IM30 triggers membrane fusion is largely unclear. IM30 monomers pre-assemble into stable tetrameric building blocks, which further align to form oligomeric ring structures, and differently sized IM30 rings bind to membranes. Based on a 3D reconstruction of IM30 rings, we locate the IM30 loop 2 region at the bottom of the ring and show intact membrane binding but missing fusogenic activity of loop 2 mutants...
August 2, 2017: Structure
https://www.readbyqxmd.com/read/28803609/comic-the-hidden-dynamics-of-mitochondrial-inner-compartments
#12
Bongki Cho, Woong Sun
Mitochondria have evolutionarily, functionally and structurally distinct outer- (OMM) and inner-membranes (IMM). Thus, mitochondrial morphology is controlled by independent but coordinated activity of fission and fusion of the OMM and IMM. Constriction and division of the OMM are mediated by endocytosis-like machineries, which include dynamin-related protein 1 with additional cytosolic vesicle scissoring machineries such as actin filament and Dynamin 2. However, structural alteration of the IMM during mitochondrial division has been poorly understood...
August 14, 2017: BMB Reports
https://www.readbyqxmd.com/read/28802158/lipidation-increases-antiviral-activities-of-coronavirus-fusion-inhibiting-peptides
#13
Jung-Eun Park, Tom Gallagher
Coronaviruses (CoVs) can cause life-threatening respiratory diseases. Their infectious entry requires viral spike (S) proteins, which attach to cell receptors, undergo proteolytic cleavage, and then refold in a process that catalyzes virus-cell membrane fusion. Fusion-inhibiting peptides bind to S proteins, interfere with refolding, and prevent infection. Here we conjugated fusion-inhibiting peptides to various lipids, expecting this to secure peptides onto cell membranes and thereby increase antiviral potencies...
August 9, 2017: Virology
https://www.readbyqxmd.com/read/28799689/fusion-and-scission-of-membranes-ubiquitous-topological-transformations-in-cells
#14
Roland L Knorr, Noboru Mizushima, Rumiana Dimova
2016 Nobel Prizes were awarded to Yoshinori Ohsumi for autophagy and to David Thouless, Duncan Haldane and Michael Kosterlitz for topological transitions. Both of these phenomena are intrinsically related when it comes to membranes. Here, we give a brief account on topological transformations of lipid membranes, commonly known as membrane fusion and membrane scission, and introduce the underlying topological invariant, the genus. The genus of a shape is a useful concept to distinguish unambiguously the processes of membrane fusion/scission and offers a simple method to describe complex, cellular membrane structures, such as fenestrated cristae...
August 11, 2017: Traffic
https://www.readbyqxmd.com/read/28797705/effects-of-hiv-1-gp41-derived-virucidal-peptides-on-virus-like-lipid-membranes
#15
Pablo Carravilla, Antonio Cruz, Itziar Martin-Ugarte, Itziar R Oar-Arteta, Johanna Torralba, Beatriz Apellaniz, Jesús Pérez-Gil, José Requejo-Isidro, Nerea Huarte, José L Nieva
Membrane fusion induced by the envelope glycoprotein enables the intracellular replication of HIV-1; hence, this process constitutes a major target for antiretroviral compounds. It has been proposed that peptides having propensity to interact with membrane interfaces might exert broad antiviral activity against enveloped viruses. To test this hypothesis, in this contribution we have analyzed the antiviral effects of peptides derived from the membrane-proximal external region and the transmembrane domain of the envelope glycoprotein subunit gp41, which display different degrees of interfacial hydrophobicity...
August 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28796901/from-peroxisomal-disorders-to-common-neurodegenerative-diseases-the-role-of-ether-phospholipids-in-the-nervous-system
#16
REVIEW
Fabian Dorninger, Sonja Forss-Petter, Johannes Berger
The emerging diverse roles of ether (phospho)lipids in nervous system development and function in health and disease are currently attracting growing interest. Plasmalogens, a subgroup of ether lipids, are important membrane components involved in vesicle fusion and membrane raft composition. They store polyunsaturated fatty acids and may serve as antioxidants. Ether lipid metabolites act as precursors for the formation of glycosyl-phosphatidyl-inositol (GPI) anchors; others, like platelet-activating factor, are implicated in signaling functions...
August 10, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28796150/the-role-of-cancer-derived-exosomes-in-tumorigenicity-epithelial-to-mesenchymal-transition
#17
REVIEW
Robert H Blackwell, Kimberly E Foreman, Gopal N Gupta
Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their basement membrane interaction and acquire a more migratory, mesenchymal phenotype. EMT has been implicated in cancer cell progression, as cells transform and increase motility and invasiveness, induce angiogenesis, and metastasize. Exosomes are 30-100 nm membrane-bound vesicles that are formed and excreted by all cell types and released into the extracellular environment. Exosomal contents include DNA, mRNA, miRNA, as well as transmembrane- and membrane-bound proteins derived from their host cell contents...
August 10, 2017: Cancers
https://www.readbyqxmd.com/read/28794270/the-golgin-protein-coy1-functions-in-intra-golgi-retrograde-transport-and-interacts-with-the-cog-complex-and-golgi-snares
#18
Nadine S Anderson, Indrani Mukherjee, Christine M Bentivoglio, Charles Barlowe
Extended coiled-coil proteins of the Golgin family play prominent roles in maintaining the structure and function of the Golgi complex. Here we further investigate the Golgin protein Coy1 and document its function in retrograde transport between early Golgi compartments. Cells that lack Coy1 displayed a reduced half-life of the Och1 mannosyltransferase, an established cargo of intra-Golgi retrograde transport. Combining the coy1Δ mutation with deletions in other putative retrograde Golgins (sgm1Δ and rud3Δ) caused strong glycosylation and growth defects and reduced membrane association of the Conserved Oligomeric Golgi complex...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28794268/force-induced-transcellular-tunnel-formation-in-endothelial-cells
#19
Win Pin Ng, Kevin D Webster, Caroline Stefani, Eva M Schmid, Emmanuel Lemichez, Patricia Bassereau, Daniel A Fletcher
The endothelium serves as a protective semipermeable barrier in blood vessels and lymphatic vessels. Leukocytes and pathogens can pass directly through the endothelium by opening holes in endothelial cells, known as transcellular tunnels, which are formed by contact and self-fusion of the apical and basal plasma membranes. Here we test the hypothesis that the actin cytoskeleton is the primary barrier to transcellular tunnel formation using a combination of atomic force microscopy and fluorescence microscopy of live cells...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28794042/palmitoylation-contributes-to-membrane-curvature-in-influenza-a-virus-assembly-and-hemagglutinin-mediated-membrane-fusion
#20
Petr Chlanda, Elena Mekhedov, Hang Waters, Alexander Sodt, Cindi Schwartz, Vinod Nair, Paul S Blank, Joshua Zimmerberg
The highly conserved cytoplasmic tail of influenza virus glycoprotein hemagglutinin (HA) contains three cysteines, post-translationally modified by covalently bound fatty acids. While viral HA acylation is crucial in virus replication, its physico-chemical role is unknown. We used virus-like particles (VLP) to study the effect of acylation on morphology, protein incorporation, lipid composition, and membrane fusion. De-acylation interrupted HA-M1 interactions since de-acylated mutant HA fail to incorporate an M1 layer within spheroidal VLP, and filamentous particles incorporated increased numbers of neuraminidase (NA)...
August 9, 2017: Journal of Virology
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