H PYLORI CAGA INHIBITS PAR1-MARK FAMILY KINASES BY MIMICKING HOST SUBSTRATES

H PYLORI CAGA 通过模仿宿主底物抑制 PAR1 标记家族激酶

• 批准号: 8361570
• 负责人: Charles Erec Stebbins
• 金额: $ 0.26万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361570
• 关键词: F2R gene; Family; Funding; Grant; Helicobacter pylori; Human; Molecular Biology; Mutagenesis; National Center for Research Resources; Nature; Peptides; Phosphotransferases; Principal Investigator; Protein Kinase Inhibitors; Proteins; Publishing; Research; Research Infrastructure; Resources; Risk; S100A8 gene; Source; Stomach Carcinoma; Structure; United States National Institutes of Health; Virulence; Work; cost; inhibitor/antagonist; macromolecule; protein kinase inhibitor; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2 This work has been published: D. Neai, M.C. Miller, Z.T. Quinkert, M. Stein, B.T. Chait, and C.E. Stebbins "Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates" Nature Structural & Molecular Biology, 17(2010)130-2

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 幽门螺杆菌的CagA蛋白与许多细胞因子相互作用，并与胃癌的毒力和风险增加有关。我们在这里提出的CagA与人类激酶PAR 1b/MARK 2的一个亚结构域的共晶结构，揭示了CagA肽模拟底物的激酶家族，类似真核蛋白激酶抑制剂。对这种相互作用起中心作用的保守残基的突变使得CagA作为MARK 2的抑制剂失活 本作品已出版： D.内爱、M.C.米勒，Z. T Quinkert，M. Stein，B.T. Chait和C.E. Stebbins“Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates”Nature Structural & Molecular Biology，17（2010）130-2