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https://www.readbyqxmd.com/read/28107566/recent-advances-in-understanding-clonal-haematopoiesis-in-aplastic-anaemia
#1
REVIEW
Natasha Stanley, Timothy S Olson, Daria V Babushok
Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic mutations and/or structural chromosomal abnormalities detected as early as at diagnosis. In contrast to other conditions linked to clonal haematopoiesis, the clonal signature of AA reflects its immune pathophysiology. The most common alterations are clonal expansions of cells lacking glycophosphotidylinositol-anchored proteins, loss of human leucocyte antigen alleles, and mutations in BCOR/BCORL1, ASXL1 and DNMT3A...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28104892/mechanistic-basis-for-a-molecular-triage-reaction
#2
Sichen Shao, Monica C Rodrigo-Brenni, Maryann H Kivlen, Ramanujan S Hegde
Newly synthesized proteins are triaged between biosynthesis and degradation to maintain cellular homeostasis, but the decision-making mechanisms are unclear. We reconstituted the core reactions for membrane targeting and ubiquitination of nascent tail-anchored membrane proteins to understand how their fate is determined. The central six-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induces rapid, private, and committed client transfer to TRC40 for successful biosynthesis...
January 20, 2017: Science
https://www.readbyqxmd.com/read/28103900/gde2-is-essential-for-neuronal-survival-in-the-postnatal-mammalian-spinal-cord
#3
Clinton Cave, Sungjin Park, Marianeli Rodriguez, Mai Nakamura, Ahmet Hoke, Mikhail Pletnikov, Shanthini Sockanathan
BACKGROUND: Glycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein that cleaves glycosylphosphatidylinositol (GPI) anchors to regulate GPI-anchored protein activity at the cell surface. In the developing spinal cord, GDE2 utilizes its enzymatic function to regulate the production of specific classes of motor neurons and interneurons; however, GDE2's roles beyond embryonic neurogenesis have yet to be defined. METHOD: Using a panel of histological, immunohistochemical, electrophysiological, behavioral, and biochemistry techniques, we characterized the postnatal Gde2 (-/-) mouse for evidence of degenerative neuropathology...
January 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28101737/spatholobus-suberectus-dunn-constituents-inhibit-sortase-a-and-staphylococcus-aureus-cell-clumping-to-fibrinogen
#4
Hyunjoo Cho, Beomkoo Chung, Chang-Kwon Kim, Dong-Chan Oh, Ki-Bong Oh, Jongheon Shin
Sortases are a family of Gram-positive transpeptidases responsible for anchoring surface protein virulence factors to the peptidoglycan cell wall layer. In Staphylococcus aureus (S. aureus), deletion of sortase isoform results in a significant reduction in virulence and infection potential. Twenty flavonoids were isolated from the stem of the folk medicinal plant Spatholobus suberectus Dunn. These compounds were tested against S. aureus-derived sortase A (SrtA), a key transpeptidase for bacterial virulence...
January 18, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28101692/the-assembly-and-function-of-perinuclear-actin-cap-in-migrating-cells
#5
Miloslava Maninova, Josef Caslavsky, Tomas Vomastek
Stress fibers are actin bundles encompassing actin filaments, actin-crosslinking, and actin-associated proteins that represent the major contractile system in the cell. Different types of stress fibers assemble in adherent cells, and they are central to diverse cellular processes including establishment of the cell shape, morphogenesis, cell polarization, and migration. Stress fibers display specific cellular organization and localization, with ventral fibers present at the basal side, and dorsal fibers and transverse actin arcs rising at the cell front from the ventral to the dorsal side and toward the nucleus...
January 18, 2017: Protoplasma
https://www.readbyqxmd.com/read/28100781/biogenesis-of-a-mitochondrial-outer-membrane-protein-in-trypanosoma-brucei-targeting-signal-and-dependence-on-an-unique-biogenesis-factor
#6
Julia Bruggisser, Sandro K Aumlser, Jan Mani, Andre Schneider
The mitochondrial outer membrane (OM) contains single and multiple membrane-spanning proteins which need to contain signals that ensure correct targeting and insertion into the OM. The biogenesis of such proteins has so far essentially only been studied in yeast and related organisms. Here we show that POMP10, an OM protein of the early diverging protozoan Trypanosoma brucei, is signal-anchored. Transgenic cells expressing variants of POMP10 fused to GFP demonstrate that the N-terminal membrane-spanning domain flanked by a few positively charged or neutral residues is both necessary and sufficient for mitochondrial targeting...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100778/structure-of-the-z-ring-associated-protein-zapd-bound-to-the-c-terminal-domain-of-the-tubulin-like-protein-ftsz-suggests-mechanism-of-z-ring-stabilization-through-ftsz-crosslinking
#7
Maria Schumacher, Kuo-Hsiang Huang, Wenjie Zeng, Anuradha Janakiraman
Cell division in most bacteria is mediated by the tubulin-like FtsZ protein, which polymerizes in a GTP-dependent manner to form the cytokinetic Z ring. A diverse repertoire of FtsZ binding proteins affect FtsZ localization and polymerization to ensure correct Z ring formation. Many of these proteins bind the C-terminal domain (CTD) of FtsZ, which serves as a hub for FtsZ regulation. FtsZ ring-associated proteins, ZapA-D (Zaps), are important FtsZ regulatory proteins that stabilize FtsZ assembly and enhance Z ring formation by increasing lateral assembly of FtsZ protofilaments, which then form the Z ring...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100636/centriole-splitting-caused-by-loss-of-the-centrosomal-linker-protein-c-nap1-reduces-centriolar-satellite-density-and-impedes-centrosome-amplification
#8
Anne-Marie Flanagan, Elena Stavenschi, Shivakumar Basavaraju, David Gaboriau, David A Hoey, Ciaran G Morrison
Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1 null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with re-expression of C-NAP1 rescuing both these phenotypes...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28096376/myosin-driven-transport-network-in-plants
#9
Elizabeth G Kurth, Valera V Peremyslov, Hannah L Turner, Kira S Makarova, Jaime Iranzo, Sergei L Mekhedov, Eugene V Koonin, Valerian V Dolja
We investigate the myosin XI-driven transport network in Arabidopsis using protein-protein interaction, subcellular localization, gene knockout, and bioinformatics analyses. The two major groups of nodes in this network are myosins XI and their membrane-anchored receptors (MyoB) that, together, drive endomembrane trafficking and cytoplasmic streaming in the plant cells. The network shows high node connectivity and is dominated by generalists, with a smaller fraction of more specialized myosins and receptors...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096354/loss-of-get-pathway-orthologs-in-arabidopsis-thaliana-causes-root-hair-growth-defects-and-affects-snare-abundance
#10
Shuping Xing, Dietmar Gerald Mehlhorn, Niklas Wallmeroth, Lisa Yasmin Asseck, Ritwika Kar, Alessa Voss, Philipp Denninger, Vanessa Aphaia Fiona Schmidt, Markus Schwarzländer, York-Dieter Stierhof, Guido Grossmann, Christopher Grefen
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095470/endogenous-semaphorin-7a-impedes-human-lung-fibroblast-differentiation
#11
Stephane Esnault, Elizabeth E Torr, Ksenija Bernau, Mats W Johansson, Elizabeth A Kelly, Nathan Sandbo, Nizar N Jarjour
Semaphorin-7A is a glycosylphosphatidylinositol-anchored protein, initially characterized as an axon guidance protein. Semaphorin-7A also contributes to immune cell regulation and may be an essential pro-fibrotic factor when expressed by non-fibroblast cell types (exogenous). In mouse models, semaphorin-7A was shown to be important for TGF-ß1-induced pulmonary fibrosis characterized by myofibroblast accumulation and extracellular matrix deposition, but the cell-specific role of semaphorin-7A was not examined in fibroblasts...
2017: PloS One
https://www.readbyqxmd.com/read/28094338/mitochondrial-protein-import-functional-analysis-of-the-highly-diverged-tom22-orthologue-of-trypanosoma-brucei
#12
Jan Mani, Samuel Rout, Silvia Desy, André Schneider
The β-barrel protein Tom40 and the α-helically anchored membrane protein Tom22 are the only universally conserved subunits of the protein translocase of the mitochondrial outer membrane (TOM). Tom22 has an N-terminal cytosolic and a C-terminal intermembrane space domain. It occurs in two variants: one typified by the yeast protein which has a cytosolic domain containing a cluster of acidic residues, and a shorter variant typified by the plant protein that lacks this domain. Yeast-type Tom22 functions as a secondary protein import receptor and is also required for the stability of the TOM complex...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090783/probing-the-druggability-of-membrane-bound-rab5-by-molecular-dynamics-simulations
#13
Eileen Edler, Matthias Stein
Rab5 is a small GTPase and a key regulator in early endosomal trafficking. Rab5 and its effectors are involved in a large number of infectious diseases and certain types of cancer. We performed µs atomistic molecular dynamics simulations of inactive and active full-length Rab5 anchored to a complex model bilayer with composition of the early endosome membrane. Direct interactions between the Rab5 G domain and the bilayer were observed. We found two dominant nucleotide-dependent orientations characterised by a different accessibility of the switch regions...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28089868/novel-calcium-recognition-constructions-in-proteins-calcium-blade-and-ef-hand-zone
#14
Alexander I Denesyuk, Sergei E Permyakov, Mark S Johnson, Eugene A Permyakov, Konstantin Denessiouk
Metal ions can regulate various cell processes being first, second or third messengers, and some of them, especially transition metal ions, take part in catalysis in many enzymes. As an intracellular ion, Ca(2+) is involved in many cellular functions from fertilization and contraction, cell differentiation and proliferation, to apoptosis and cancer. Here, we have identified and described two novel calcium recognition environments in proteins: the calcium blade zone and the EF-hand zone, common to 12 and 8 different protein families, respectively...
January 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28089452/co-folding-of-a-flif-flig-split-domain-forms-the-basis-of-the-ms-c-ring-interface-within-the-bacterial-flagellar-motor
#15
Michael J Lynch, Robert Levenson, Eun A Kim, Ria Sircar, David F Blair, Frederick W Dahlquist, Brian R Crane
The interface between the membrane (MS) and cytoplasmic (C) rings of the bacterial flagellar motor couples torque generation to rotation within the membrane. The structure of the C-terminal helices of the integral membrane protein FliF (FliFC) bound to the N terminal domain of the switch complex protein FliG (FliGN) reveals that FliGN folds around FliFC to produce a topology that closely resembles both the middle and C-terminal domains of FliG. The interface is consistent with solution-state nuclear magnetic resonance, small-angle X-ray scattering, in vivo interaction studies, and cellular motility assays...
December 31, 2016: Structure
https://www.readbyqxmd.com/read/28089327/ceruloplasmin-gene-expression-profile-changes-in-the-rat-mammary-gland-during-pregnancy-lactation-and-involution
#16
Natalia A Platonova, Iurii A Orlov, Sergey A Klotchenko, Victor S Babich, Ekaterina Y Ilyechova, Polina S Babich, Yuri P Garmai, Andrey V Vasin, Nadezhda V Tsymbalenko, Liudmila V Puchkova
Copper metabolism disturbances in mammary gland (MG) cells have severe consequences in newborns. The mechanism that controls the balance of copper in the MG has not been thoroughly characterized. Four primary copper homeostasis genes in mammals: (1) ceruloplasmin (Cp) encoding multifunction multicopper blue (ferr)oxidase; (2) CTR1 encoding high affinity copper importer 1; and (3 and 4) two similar genes encoding Cu(I)/Cu(II)-ATPases P1 type (ATP7A and ATP7B) responsible for copper efflux from the cells and metallation of cuproenzymes formed in the Golgi complex are expressed in MG...
January 3, 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28078525/chitosan-ceramide-coating-on-gold-nanorod-to-improve-its-physiological-stability-and-reduce-the-lipid-surface-related-toxicity
#17
Gantumur Battogtokh, Oyuntuya Gotov, Young Tag Ko
Gold nanoparticles are promising materials for many applications that include imaging, drug delivery, and photothermal therapy. However, AuNPs can be unstable and/or toxic. We purposed to improve the stability and reduce toxicity of gold nanorods (AuNR) upon coating with biocompatible polymer, chitosan-ceramide (CS-CE), without replacing the original layer, CTAB. CS-CE-coated AuNR was prepared by simple mixing for 24 h and purified by centrifugation. The coating was confirmed by UV-Vis absorption analysis and surface charge and size measurement...
January 11, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28078417/covalent-organic-framework-coated-magnetic-graphene-as-a-novel-support-for-trypsin-immobilization
#18
Heping Wang, Fenglong Jiao, Fangyuan Gao, Xinyuan Zhao, Yan Zhao, Yehua Shen, Yangjun Zhang, Xiaohong Qian
Deep and efficient proteolysis is the critical premise in mass spectrometry-based bottom-up proteomics. It is difficult for traditional in-solution digestion to meet the requirement unless prolonged digestion time and enhanced enzyme dosage are employed, which makes the whole workflow time-consuming and costly. The abovementioned problems could be effectively ameliorated by anchoring many proteases on solid supports. In this work, covalent organic framework-coated magnetic graphene (MG@TpPa-1) was designed and prepared as a novel enzyme carrier for the covalent immobilization of trypsin with a high degree of loading (up to 268 μg mg(-1))...
January 11, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28078416/poly-ethylene-glycol-functionalization-of-monolithic-poly-divinyl-benzene-for-improved-miniaturized-solid-phase-extraction-of-protein-rich-samples
#19
Esme Candish, Aminreza Khodabandeh, Marianne Gaborieau, Thomas Rodemann, Robert A Shellie, Andrew A Gooley, Emily F Hilder
Non-specific protein adsorption on hydrophobic solid phase extraction (SPE) adsorbents can reduce the efficacy of purification. To improve sample clean-up, poly(divinyl benzene) (PDVB) monoliths grafted with hydrophilic polyethylene glycol methacrylate (PEGMA) were developed. Residual vinyl groups (RVGs) of the PDVB were employed as anchor points for PEGMA grafting. Two PEGMA monomers, M n 360 and 950, were compared for graft solutions containing 5-20% monomer. Protein binding was qualitatively screened using fluorescently labeled human serum albumin (HSA) to determine optimal PEGMA concentration...
January 11, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28077875/structural-basis-of-co-translational-quality-control-by-arfa-and-rf2-bound-to-ribosome
#20
Fuxing Zeng, Yanbo Chen, Jonathan Remis, Mrinal Shekhar, James C Phillips, Emad Tajkhorshid, Hong Jin
Quality control mechanisms intervene appropriately when defective translation events occur, in order to preserve the integrity of protein synthesis. Rescue of ribosomes translating on messenger RNAs that lack stop codons is one of the co-translational quality control pathways. In many bacteria, ArfA recognizes stalled ribosomes and recruits the release factor RF2, which catalyses the termination of protein synthesis. Although an induced-fit mechanism of nonstop mRNA surveillance mediated by ArfA and RF2 has been reported, the molecular interaction between ArfA and RF2 in the ribosome that is responsible for the mechanism is unknown...
January 11, 2017: Nature
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