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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 幽门螺杆菌的CagA蛋白与多种细胞因子相互作用，与提高幽门螺杆菌的毒力和胃癌的风险有关。我们在这里展示了CagA的一个亚域与人的激酶PAR1b/Mark2的共晶体结构，揭示了CagA的一个多肽模拟该激酶家族的底物，类似于真核蛋白激酶抑制剂。这种相互作用中心的保守残基的突变使CagA失去作为Mark2抑制物的活性

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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