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https://www.readbyqxmd.com/read/28108595/identification-of-the-adpr-binding-pocket-in-the-nudt9-homology-domain-of-trpm2
#1
Peilin Yu, Xiwen Xue, Jianmin Zhang, Xupang Hu, Yan Wu, Lin-Hua Jiang, Hongwei Jin, Jianhong Luo, Liangren Zhang, Zhenming Liu, Wei Yang
Activation of the transient receptor potential melastatin 2 (TRPM2) channel occurs during the response to oxidative stress under physiological conditions as well as in pathological processes such as ischemia and diabetes. Accumulating evidence indicates that adenosine diphosphate ribose (ADPR) is the most important endogenous ligand of TRPM2. However, although it is known that ADPR binds to the NUDT9 homology (NUDT9-H) domain in the intracellular C-terminal region, the molecular mechanism underlying ADPR binding and activation of TRPM2 remains unknown...
January 20, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28107768/arabidopsis-protein-s-acyl-transferase4-mediates-root-hair-growth
#2
Zhi-Yuan Wan, Sen Chai, Fu-Rong Ge, Qiang-Nan Feng, Yan Zhang, Sha Li
Polar growth of root hairs is critical for plant survival and necessitates fine-tuned ROP signaling. Multiple ROP regulators participate in root hair growth. However, protein S-acyl transferases (PATs), mediating the S-acylation and membrane partitioning of ROPs, are yet to be found. By using a reverse genetic approach, combining fluorescence probes, pharmacological drugs, site-directed mutagenesis, and genetic analysis with related root-hair mutants, we have identified and characterized an Arabidopsis PAT, which may be responsible for ROP2 S-acylation in root hairs...
January 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28106071/development-of-an-efficient-screening-system-to-identify-novel-bone-metabolism-related-genes-using-the-exchangeable-gene-trap-mutagenesis-mouse-models
#3
Syuji Kurogi, Tomohisa Sekimoto, Taro Funamoto, Tomomi Ota, Shihoko Nakamura, Takuya Nagai, Mai Nakahara, Kumiko Yoshinobu, Kimi Araki, Masatake Araki, Etsuo Chosa
Despite numerous genetic studies on bone metabolism, understanding of the specific mechanisms is lacking. We developed an efficient screening system to identify novel genes involved in bone metabolism using mutant mouse strains registered with the Exchangeable Gene Trap Clones (EGTC) database. From 1278 trap clones in the EGTC database, 52 candidate lines were selected in the first screening, determined based on "EST profile", "X-gal", "Related article", and "Novel gene". For the second screening, bone morphometric analysis, biomechanical strength analysis, bone X-gal staining, etc...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105914/homology-modeling-and-molecular-dynamics-provide-structural-insights-into-tospovirus-nucleoprotein
#4
Rayane Nunes Lima, Muhammad Faheem, João Alexandre Ribeiro Gonçalves Barbosa, Marcelo Depólo Polêto, Hugo Verli, Fernando Lucas Melo, Renato Oliveira Resende
BACKGROUND: Tospovirus is a plant-infecting genus within the family Bunyaviridae, which also includes four animal-infecting genera: Hantavirus, Nairovirus, Phlebovirus and Orthobunyavirus. Compared to these members, the structures of Tospovirus proteins still are poorly understood. Despite multiple studies have attempted to identify candidate N protein regions involved in RNA binding and protein multimerization for tospovirus using yeast two-hybrid systems (Y2HS) and site-directed mutagenesis, the tospovirus ribonucleocapsids (RNPs) remains largely uncharacterized at the molecular level and the lack of structural information prevents detailed insight into these interactions...
December 15, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28105689/preferential-recognition-of-auto-antibodies-against-4-hydroxynonenal-modified-dna-in-the-cancer-patients
#5
Mohammad Faisal, Uzma Shahab, Abdulrahman A Alatar, Saheem Ahmad
BACKGROUND: The structural perturbations in DNA molecule may be caused by a break in a strand, a missing base from the backbone, or a chemically changed base. These alterations in DNA that occurs naturally can result from metabolic or hydrolytic processes. DNA damage plays a major role in the mutagenesis, carcinogenesis, aging and various other patho-physiological conditions. DNA damage can be induced through hydrolysis, exposure to reactive oxygen species (ROS) and other reactive carbonyl metabolites including 4-hydroxynonenal (HNE)...
January 20, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28104757/analysis-and-identification-of-the-grem2-heparin-heparan-sulfate-binding-motif
#6
Chandramohan Kattamuri, Kristof Nolan, Thomas B Thompson
Bone Morphogenetic Proteins (BMP) are regulated by extracellular antagonists of the DAN (differential screening selected gene aberrative in neuroblastoma) family. Similar to the BMP ligands, certain DAN family members have been shown to interact with heparin and heparan sulfate (HS). Structural studies of DAN family members Gremlin-1 and Gremlin-2 have revealed a dimeric growth-factor like fold where a series of lysine residues cluster along one face of the protein. In this study, we used mutagenesis, heparin binding measurements, and cell surface binding analysis to identify lysine residues that are important for heparin/HS binding in Gremlin-2...
January 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28104755/n-glycosylation-of-human-sphingomyelin-phosphodiesterase-acid-like-3a-smpdl3a-is-essential-for-stability-secretion-and-activity
#7
Mathew Traini, Raani Kumaran, Morten Thaysen-Andersen, Maaike Kockx, Wendy Jessup, Leonard Kritharides
Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a recently identified phosphodiesterase, which is a secreted N -linked glycoprotein. SMPDL3A is highly homologous to acid sphingomyelinase (aSMase), but unlike aSMase can not cleave sphingomyelin. Rather, SMPDL3A hydrolyzes nucleotide tri- and diphosphates and their derivatives. While recent structural studies have shed light on these unexpected substrate preferences, many other aspects of SMPDL3A biology which may give insight into its function in vivo remain obscure...
January 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28103689/structure-and-function-of-a-c-c-bond-cleaving-oxygenase-in-atypical-angucycline-biosynthesis
#8
Guohui Pan, Xiaoqin Gao, Keqiang Fan, Junlin Liu, Bing Meng, Jinmin Gao, Bin Wang, Chaobo Zhang, Hui Han, Guomin Ai, Yihua Chen, Dong Wu, Zhi-Jie Liu, Keqian Yang
C-C bond ring cleaving oxygenases represent a unique family of enzymes involved in the B ring cleavage reaction only observed in atypical angucycline biosynthesis. B ring cleavage is the key reaction leading to dramatic divergence in the final structures of atypical angucyclines. Here, we present the crystal structure of AlpJ, the first structure of this family of enzymes. AlpJ has been verified as the enzyme catalyzing C-C bond cleavage in kinamycin biosynthesis. The crystal structure of the AlpJ monomer resembles the dimeric structure of ferredoxin-like proteins...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28103683/simultaneous-targeting-of-npc1-and-vdac1-by-itraconazole-leads-to-synergistic-inhibition-of-mtor-signaling-and-angiogenesis
#9
Sarah A Head, Wei Q Shi, Eun Ju Yang, Benjamin A Nacev, Sam Y Hong, Kalyan K Pasunooti, Ruo-Jing Li, Joong Sup Shim, Jun O Liu
The antifungal drug itraconazole was recently found to exhibit potent antiangiogenic activity and has since been repurposed as an investigational anticancer agent. Itraconazole has been shown to exert its antiangiogenic activity through inhibition of the mTOR signaling pathway, but the molecular mechanism of action was unknown. We recently identified the mitochondrial protein VDAC1 as a target of itraconazole and a mediator of its activation of AMPK, an upstream regulator of mTOR. However, VDAC1 could not account for the previously reported inhibition of cholesterol trafficking by itraconazole, which was also demonstrated to lead to mTOR inhibition...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28103122/ptk2-mediated-degradation-of-atg3-impedes-cancer-cells-susceptible-to-dna-damage-treatment
#10
Ke Ma, Wan Fu, Ming Tang, Chaohua Zhang, Tianyun Hou, Ran Li, Xiaopeng Lu, Yanan Wang, Jingyi Zhou, Xue Li, Luyao Zhang, Lina Wang, Ying Zhao, Wei-Guo Zhu
ATG3 (autophagy related 3) is an E2-like enzyme essential for autophagy; however, it is unknown whether it has an autophagy-independent function. Here, we report that ATG3 is a relatively stable protein in unstressed cells, but it is degraded in response to DNA-damaging agents such as etoposide or cisplatin. With mass spectrometry and a mutagenesis assay, phosphorylation of tyrosine 203 of ATG3 was identified to be a critical modification for its degradation, which was further confirmed by manipulating ATG3(Y203E) (phosphorylation mimic) or ATG3(Y203F) (phosphorylation-incompetent) in Atg3 knockout MEFs...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28102911/glutathione-peroxidase-like-enzymes-cover-five-distinct-cell-compartments-and-membrane-surfaces-in-arabidopsis-thaliana
#11
Safira Attacha, David Solbach, Krisztina Bela, Anna Moseler, Stephan Wagner, Markus Schwarzländer, Isabel Aller, Stefanie J Müller, Andreas J Meyer
Glutathione peroxidase-like enzymes (GPXLs) constitute a family of eight peroxidases in Arabidopsis thaliana. In contrast to the eponymous selenocysteine glutathione peroxidases (GPXs) in mammalian cells which use glutathione as electron donor, GPXLs rely on cysteine instead of selenocysteine for activity and depend on the thioredoxin system for reduction. Although plant GPXLs have been implicated in important agronomic traits such as drought tolerance, photooxidative tolerance and immune responses there remain major ambiguities regarding their subcellular localization...
January 19, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28102671/structural-analysis-of-glycosylated-intact-hiv-1-gp120-b12-antibody-complex-using-hydroxyl-radical-protein-footprinting
#12
Xiaoyan Li, Oliver C Grant, Keigo Ito, Aaron Wallace, Shixia Wang, Peng Zhao, Lance Wells, Shan Lu, Robert J Woods, Joshua S Sharp
Glycoprotein gp120 is a surface antigen and virulence factor of the human immunodeficiency virus-1 (HIV-1). Broadly neutralizing antibodies (bNAbs) that are reactive to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system due to its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28101696/role-of-the-helix-in-talin-f3-domain-f3-helix-in-talin-mediated-integrin-activation
#13
Ang Li, Qiang Guo, Ailin Wei, Yaliang Zhou, Weiming Hu
Increases in ligand binding to cellular integrins (activation) play an important role in platelet and leukocyte function. Talin is necessary in vivo and sufficient in vitro for integrin αIIbβ3 activation. The precise mechanisms by which talin activates integrin are still being elucidated. In particular, talin undergoes conformational changes (around the F3 helix) and inserts the F3 helix into lipid bilayer; however, the connection between this lipid-inserting mechanism of talin and talin's capacity to activate integrin has never been explored before...
January 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28100785/protein-kinase-c-controls-binding-of-igo-ensa-proteins-to-protein-phosphatase-2a-in-budding-yeast
#14
Vu Thai, Noah Dephoure, Amit Weiss, Jacqueline Ferguson, Ricardo Leitao, Steven P Gygi, Douglas R Kellogg
Protein phosphatase 2A (PP2A) plays important roles in controlling mitosis in all eukaryotic cells. The form of PP2A that controls mitosis is associated with a conserved regulatory subunit that is called B55 in vertebrates and Cdc55 in budding yeast. The activity of this form of PP2A can be inhibited by binding of conserved Igo/ENSA proteins. Although the mechanisms that activate Igo/ENSA to bind to PP2A are well understood, little is known about how they are inactivated. Here, we have analyzed regulation of Igo/ENSA in the context of a checkpoint pathway that links mitotic entry to membrane growth in budding yeast...
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
#15
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/28100651/stabilization-of-bacillus-circulans-xylanase-by-combinatorial-insertional-fusion-to-a-thermophilic-host-protein
#16
Vandan Shah, Brennal Pierre, Tamari Kirtadze, Seung Shin, Jin Ryoun Kim
High thermostability of an enzyme is critical for its industrial application. While many engineering approaches such as mutagenesis have enhanced enzyme thermostability, they often suffer from reduced enzymatic activity. A thermally stabilized enzyme with unchanged amino acids is preferable for subsequent functional evolution necessary to address other important industrial needs. In the research presented here, we applied insertional fusion to a thermophilic maltodextrin-binding protein from Pyrococcus furiosus (PfMBP) in order to improve the thermal stability of Bacillus circulans xylanase (BCX)...
January 17, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28100616/the-v3-loop-of-hiv-1-env-determines-viral-susceptibility-to-ifitm3-impairment-of-viral-infectivity
#17
Yimeng Wang, Qinghua Pan, Shilei Ding, Zhen Wang, Jingyou Yu, Andrés Finzi, Shan-Lu Liu, Chen Liang
: Interferon inducible transmembrane proteins (IFITMs) inhibit a broad spectrum of viruses including HIV-1. IFITM proteins deter HIV-1 entry when expressed in target cells and also impair HIV-1 infectivity when expressed in virus producer cells. However, little is known about how viruses resist IFITM inhibition. In this study, we have investigated the susceptibilities of different primary isolates of HIV-1 to the inhibition of viral infectivity by IFITMs. Our results demonstrate that the infectivity of different HIV-1 primary isolates including transmitted founder viruses is diminished by IFITM3 to various levels, with strain AD8-1 exhibiting strong resistance...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100609/sterol-binding-by-the-tombusviral-replication-proteins-is-essential-for-replication-in-yeast-and-plants
#18
Kai Xu, Peter D Nagy
: Membranous structures derived from various organelles are important for replication of plus-stranded RNA viruses. Although the important roles of co-opted host proteins in RNA virus replication have been appreciated for a decade, the equally important functions of cellular lipids in virus replication are gaining full attention only recently. Previous works with Tomato bushy stunt tombusvirus (TBSV) in model host yeast have revealed essential roles for phosphatidylethanolamine and sterols in viral replication...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100588/involvement-of-conserved-amino-acids-in-the-c-terminal-region-of-line-1-orf2p-in-retrotransposition
#19
Claiborne M Christian, Mark Sokolowski, Dawn deHaro, Kristine J Kines, Victoria P Belancio
Long Interspersed Element 1 (LINE-1 or L1) is the only currently active autonomous retroelement in the human genome. Along with the parasitic SVA and SINE Alu, L1 is the source of DNA damage induced by retrotransposition, a copy-and-paste process that has the potential to disrupt gene function and cause human disease. The retrotransposition process is dependent upon the ORF2 protein (ORF2p). However, it is unknown whether most of the protein is important for retrotransposition. In particular, other than the Cys motif, the C-terminus of the protein has not been intensely examined in the context of retrotransposition...
January 18, 2017: Genetics
https://www.readbyqxmd.com/read/28099845/absence-of-neurofibromin-induces-an-oncogenic-metabolic-switch-via-mitochondrial-erk-mediated-phosphorylation-of-the-chaperone-trap1
#20
Ionica Masgras, Francesco Ciscato, Anna Maria Brunati, Elena Tibaldi, Stefano Indraccolo, Matteo Curtarello, Federica Chiara, Giuseppe Cannino, Elena Papaleo, Matteo Lambrughi, Giulia Guzzo, Alberto Gambalunga, Marco Pizzi, Vincenza Guzzardo, Massimo Rugge, Stefania Edith Vuljan, Fiorella Calabrese, Paolo Bernardi, Andrea Rasola
Mutations in neurofibromin, a Ras GTPase-activating protein, lead to the tumor predisposition syndrome neurofibromatosis type 1. Here, we report that cells lacking neurofibromin exhibit enhanced glycolysis and decreased respiration in a Ras/ERK-dependent way. In the mitochondrial matrix of neurofibromin-deficient cells, a fraction of active ERK1/2 associates with succinate dehydrogenase (SDH) and TRAP1, a chaperone that promotes the accumulation of the oncometabolite succinate by inhibiting SDH. ERK1/2 enhances both formation of this multimeric complex and SDH inhibition...
January 17, 2017: Cell Reports
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