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membrane protein folding

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https://www.readbyqxmd.com/read/27923041/crystal-structure-of-the-salmonella-typhimurium-effector-gtge
#1
Caishuang Xu, Guennadi Kozlov, Kathy Wong, Kalle Gehring, Miroslaw Cygler
Salmonella Typhimurium GtgE is an effector protein contributing to the virulence of this pathogen. It was shown to possess highly selective proteolytic activity against a subset of Rab proteins that helps in evasion of Salmonella-containing vacuole (SCV) fusion with lysosomes. Cys45, His151 and Asp169 are essential for proteolytic activity. The structure of a C-terminal fragment GtgE(79-214) indicated the presence of a papain-like fold. Here, we present the structure of GtgE(17-214) containing the fully assembled active site...
2016: PloS One
https://www.readbyqxmd.com/read/27920818/exposition-of-hepatitis-b-surface-antigen-hbsag-on-the-surface-of-hek293t-cell-and-evaluation-of-its-expression
#2
Mina Mirian, Razieh Taghizadeh, Hossein Khanahmad, Mansour Salehi, Ali Jahanian-Najafabadi, Hojjat Sadeghi-Aliabadi, Shirin Kouhpayeh
Hepatitis B virus (HBV) is considered as a global health concern and hepatitis B surface antigen (HBsAg) is the most immunogenic protein of HBV. The purpose of this study was to evaluate the expression of HBsAg on the cell surface of human embryonic kidney cell line (HEK293T). After transformation of expression vector pcDNA/HBsAg to E.coli TOP10F', plasmid was extracted and digested with BglII. Afterwards, the linearized vector was transfected to cells and treated with hygromycin B for 5 weeks to expand the resulted clonies...
October 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27918825/early-postnatal-hyperoxia-in-mice-leads-to-severe-persistent-vitreoretinopathy
#3
Paul G McMenamin, Rachel Kenny, Sjakon Tahija, Jeremiah Lim, Cecilia Naranjo Golborne, Xiangting Chen, Sheena Bouch, Foula Sozo, Bang Bui
Purpose: To describe a mouse model of hyperoxia-induced vitreoretinopathy that replicated some of the clinical and pathologic features encountered in infants with severe retinopathy of prematurity and congenital ocular conditions such as persistent hyperplastic primary vitreous. Methods: Experimental mice (C57BL/6J) were exposed to 65% oxygen between postnatal days (P)0 to P7 and studied at P10, P14, and 3, 5, 8, 20, and 40 weeks. Controls were exposed to normoxic conditions...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27914200/assembling-the-tat-protein-translocase
#4
Felicity Alcock, Phillip J Stansfeld, Hajra Basit, Johann Habersetzer, Matthew Ab Baker, Tracy Palmer, Mark I Wallace, Ben C Berks
The twin-arginine protein translocation system (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membranes of plant chloroplasts. The Tat transporter is assembled from multiple copies of the membrane proteins TatA, TatB, and TatC. We combine sequence co-evolution analysis, molecular simulations, and experimentation to define the interactions between the Tat proteins of Escherichia coli at molecular-level resolution. In the TatBC receptor complex the transmembrane helix of each TatB molecule is sandwiched between two TatC molecules, with one of the inter-subunit interfaces incorporating a functionally important cluster of interacting polar residues...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27914199/filamin-a-synaptic-organizer-in-drosophila-determines-glutamate-receptor-composition-and-membrane-growth
#5
GaYoung Lee, Thomas L Schwarz
Filamin is a scaffolding protein that functions in many cells as an actin-crosslinker. FLN90, an isoform of the Drosophila ortholog Filamin/cheerio that lacks the actin-binding domain, is here shown to govern the growth of postsynaptic membrane folds and the composition of glutamate receptor clusters at the larval neuromuscular junction. Genetic and biochemical analyses revealed that FLN90 is present surrounding synaptic boutons. FLN90 is required in the muscle for localization of the kinase dPak and, downstream of dPak, for localization of the GTPase Ral and the exocyst complex to this region...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27912985/immunogenicity-and-malaria-transmission-reducing-potency-of-pfs48-45-and-pfs25-encoded-by-dna-vaccines-administered-by-intramuscular-electroporation
#6
Dibyadyuti Datta, Geetha P Bansal, Dietlind L Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses...
November 29, 2016: Vaccine
https://www.readbyqxmd.com/read/27911771/stability-folding-dynamics-and-long-range-conformational-transition-of-the-synaptic-t-snare-complex
#7
Xinming Zhang, Aleksander A Rebane, Lu Ma, Feng Li, Junyi Jiao, Hong Qu, Frederic Pincet, James E Rothman, Yongli Zhang
Synaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) couple their stepwise folding to fusion of synaptic vesicles with plasma membranes. In this process, three SNAREs assemble into a stable four-helix bundle. Arguably, the first and rate-limiting step of SNARE assembly is the formation of an activated binary target (t)-SNARE complex on the target plasma membrane, which then zippers with the vesicle (v)-SNARE on the vesicle to drive membrane fusion. However, the t-SNARE complex readily misfolds, and its structure, stability, and dynamics are elusive...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909893/osteogain%C3%A2-loaded-onto-an-absorbable-collagen-sponge-induces-attachment-and-osteoblast-differentiation-of-st2-cells-in-vitro
#8
Richard J Miron, Masako Fujioka-Kobayashi, Yufeng Zhang, Anton Sculean, Benjamin Pippenger, Yoshinori Shirakata, Umadevi Kandalam, Maria Hernandez
OBJECTIVES: Dimensional changes of the alveolar bone following tooth extraction are a major challenge in daily dental practice. To limit bone loss, a variety of biomaterials including bone grafts, barrier membranes, and growth factors have been utilized either alone or in combination therapies to increase the speed and quality of new bone formation. The aim of the present in vitro study was to investigate the regenerative potential of Osteogain®, a new liquid carrier system of enamel matrix derivative (EMD) in combination with an absorbable collagen sponge (ACS) specifically designed for extraction socket healing...
December 1, 2016: Clinical Oral Investigations
https://www.readbyqxmd.com/read/27907150/molecular-characterization-of-two-monoclonal-antibodies-against-the-same-epitope-on-b-cell-receptor-associated-protein-31
#9
Won-Tae Kim, Saemina Shin, Hyo Jeong Hwang, Min Kyu Kim, Han-Sung Jung, Hwangseo Park, Chun Jeih Ryu
Previously, we showed that B-cell receptor associated protein 31 (BAP31), an endoplasmic reticulum (ER) membrane chaperone, is also expressed on the cell surface by two monoclonal antibodies (MAbs) 297-D4 and 144-A8. Both MAbs recognize the same linear epitope on the C-terminal domain of BAP31, although they were independently established. Here, flow cytometric analysis showed that 144-A8 had additional binding properties to some cells, as compared to 297-D4. Quantitative antigen binding assays also showed that 144-A8 had higher antigen binding capacity than 297-D4...
2016: PloS One
https://www.readbyqxmd.com/read/27904144/causes-and-consequences-of-endoplasmic-reticulum-stress-in-rheumatic-disease
#10
REVIEW
Fatemeh Navid, Robert A Colbert
Rheumatic diseases represent a heterogeneous group of inflammatory conditions, many of which involve chronic activation of both innate and adaptive immune responses by multiple genetic and environmental factors. These immune responses involve the secretion of excessive amounts of cytokines and other signalling mediators by activated immune cells. The endoplasmic reticulum (ER) is the cellular organelle that directs the folding, processing and trafficking of membrane-bound and secreted proteins, including many key components of the immune response...
December 1, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#11
Teresa M Buck, Alexa S Jordahl, Megan E Yates, Mike Preston, Emily Cook, Thomas R Kleyman, Jeffrey L Brodsky
The Epithelial Sodium Channel (ENaC) in kidney regulates blood pressure through control of sodium and volume homeostasis, and in lung ENaC regulates the volume of airway and alveolar fluids.  ENaC is a heterotrimer of homologous α-, β-, and γ-subunits, and assembles in the Endoplasmic Reticulum (ER) before it traffics and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γENaC, for degradation when the ENaC subunits were individually expressed...
November 30, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27903652/prepore-stability-controls-productive-folding-of-the-bam-independent-multimeric-outer-membrane-secretin-puld
#12
Ingrid Guilvout, Sébastien Brier, Mohamed Chami, Véronique Hourdel, Olivera Francetic, Anthony P Pugsley, Julia Chamot-Rooke, Gerard H M Huysmans
Members of a group of multimeric secretion pores that assemble independently of any known membrane-embedded insertase in Gram-negative bacteria fold into a prepore before membrane-insertion occurs. The mechanisms and the energetics that drive the folding of these proteins are poorly understood. Here, equilibrium unfolding and hydrogen/deuterium exchange monitored by mass spectrometry indicated that a loss of 4-5 kJ/mol/protomer in the N3-domain that is peripheral to the membrane-spanning C-domain in the dodecameric secretin PulD, the founding member of this class, prevents pore formation by destabilizing the prepore into a poorly structured dodecamer as visualized by electron microscopy...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27894013/outer-membrane-protein-design
#13
REVIEW
Joanna Sg Slusky
Membrane proteins are the gateway to the cell. These proteins are also a control center of the cell, as information from the outside is passed through membrane proteins as signals to the cellular machinery. The design of membrane proteins seeks to harness the power of these gateways and signal carriers. This review will focus on the design of the membrane proteins that are in the outer membrane, a membrane which only exists for gram negative bacteria, mitochondria, and chloroplasts. Unlike other membrane proteins, outer membrane proteins are uniquely shaped as β-barrels...
November 25, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27892646/trafficking-of-pfexp1-to-the-parasitophorous-vacuolar-membrane-of-plasmodium-falciparum-is-independent-of-protein-folding-and-the-ptex-translocon
#14
Anke Tribensky, Andreas W Graf, Mathias Diehl, Wiebke Fleck, Jude M Przyborski
Having entered the mature human erythrocyte, the malaria parasite survives and propagates within a parasitophorous vacuole (PV), a membrane-bound compartment separating the parasite from the host cell cytosol. The bounding membrane of this vacuole, referred to as the parasitophorous vacuolar membrane (PVM), contains parasite-encoded proteins, but how these membrane proteins are trafficked to the PVM remains unknown. Here we have studied the trafficking of PfExp1 to the PVM. We find that trafficking of PfExp1 to the PVM is independent of the folding state of the protein, and also continues unabated upon inactivation of the PVM translocon PTEX...
November 28, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27890399/a-partially-purified-outer-membrane-protein-virb9-1-for-low-cost-nanovaccines-against-anaplasma-marginale
#15
Liang Zhao, Antonino S Cavallaro, David Wibowo, Bing Zhang, Jun Zhang, Neena Mitter, Chengzhong Yu, Chun-Xia Zhao, Anton P J Middelberg
Anaplasma marginale is a devastating tick-borne pathogen causing anaplasmosis in cattle and results in significant economic loss to the cattle industry worldwide. Currently, there is no widely accepted vaccine against A. marginale. New generation subunit vaccines against A. marginale, which are much safer, more efficient and cost-effective, are in great need. The A. marginale outer membrane protein VirB9-1 is a promising antigen for vaccination. We previously have shown that soluble recombinant VirB9-1 protein can be expressed and purified from Escherichia coli and induce a high level of humoral and cellular immunity in mice...
November 24, 2016: Vaccine
https://www.readbyqxmd.com/read/27888074/toxoplasma-gondii-immune-mapped-protein-1-is-anchored-to-the-inner-leaflet-of-the-plasma-membrane-and-adopts-a-novel-protein-fold
#16
Yonggen Jia, Stefi Benjamin, Qun Liu, Yingqi Xu, Sunil Kumar Dogga, Jing Liu, Stephen Matthews, Dominique Soldati-Favre
The immune mapped protein 1 (IMP1) was first identified as a protective antigen in Eimeria maxima and described as vaccine candidate and invasion factor in Toxoplasma gondii. We show here that TgIMP1 localizes to the inner leaflet of plasma membrane (PM) via dual acylation. Mutations either in the N-terminal myristoylation or palmitoylation sites (G2 and C5) cause relocalization of TgIMP1 to the cytosol. The first 11 amino acids are sufficient for PM targeting and the presence of lysine (K7) is critical. Disruption of TgIMP1 gene by double homologous recombination revealed no invasion defect or any measurable alteration in the lytic cycle of tachyzoites...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27887849/inhibition-of-heat-shock-protein-hsp-90-potentiates-the-antiproliferative-and-pro-apoptotic-effects-of-2-4-fluoro-phenylamino-4h-1-3-thiazine-6-5-b-indole-in-a2780cis-cells
#17
Zuzana Solárová, Martin Kello, Lenka Varinská, Mariana Budovská, Peter Solár
Ovarian carcinoma is initially sensitive to platinum-based therapy, but become resistant over time. The study of cancer sensitizing substance is therefore the major challenge for a number of scientific groups. Our experiments were carried out on human ovarian adenocarcinoma A2780cis cells resistant to cisplatin and their response to 2-(4'fluoro-phenylamino)-4H-1,3-thiazine[6,5-b]indole (thiazine[6,5-b]indole) and/or heat shock protein (Hsp) 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) using proliferation assay, cell cycle analysis and monitoring of apoptosis were examined...
November 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27887588/longitudinal-reference-ranges-for-maternal-plasma-laeverin-and-its-role-as-a-potential-biomarker-of-preeclampsia
#18
Mona Nystad, Vasilis Sitras, Kari Flo, Christian Widnes, Åse Vårtun, Tom Wilsgaard, Ganesh Acharya
BACKGROUND: Laeverin is a placenta-specific membrane-bound aminopeptidase. In this study we wanted to: 1) serially measure plasma levels of laeverin in healthy women during the second half of pregnancy and postpartum, 2) determine whether laeverin is differently expressed at 22-24 weeks in women who later develop preeclampsia compared to controls, 3) compare laeverin protein expression in placenta and umbilical vein serum in healthy and preeclamptic pregnancies at birth. METHODS: Plasma was obtained serially, approximately every 4-weeks, from 53 healthy women with uncomplicated pregnancies during 22(+0) to 39(+6) weeks of gestation, and at 22-24 weeks from 15 women who later developed preeclampsia...
November 25, 2016: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/27884598/coiled-coils-a-model-system-for-the-21st-century
#19
REVIEW
Andrei N Lupas, Jens Bassler
α-Helical coiled coils were described more than 60 years ago as simple, repetitive structures mediating oligomerization and mechanical stability. Over the past 20 years, however, they have emerged as one of the most diverse protein folds in nature, enabling many biological functions beyond mechanical rigidity, such as membrane fusion, signal transduction, and solute transport. Despite this great diversity, their structures can be described by parametric equations, making them uniquely suited for rational protein design...
November 21, 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27884423/alterations-in-a-unique-class-of-cortical-chandelier-cell-axon-cartridges-in-schizophrenia
#20
Brad R Rocco, Adam M DeDionisio, David A Lewis, Kenneth N Fish
BACKGROUND: The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABAA receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs...
September 29, 2016: Biological Psychiatry
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