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首页> 外文期刊>Journal of Cellular Physiology >In vivo identification of the interaction site of ErbB2 extracellular domain with its autoinhibitor.
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In vivo identification of the interaction site of ErbB2 extracellular domain with its autoinhibitor.

机译:体内的交互网站的识别ErbB2细胞外领域的

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Direct interference with the transforming potential of ErbB2 has become a subject of great interest. Disruption of critical ErbB2 ectodomain interactions may lead to novel therapeutic approaches for the treatment of various tumors. The ErbB receptor signaling can be inhibited by rationally designed peptide mimetics based on the subdomains of ErbB ectodomain. The mimetics can bind to the ErbB receptor specifically and block inter-receptor interactions, resulting in the growth inhibition of ErbB2-overexpressing cells in vitro. In this study, three-dimensional structure of herstatin, an autoinhibitor of ErbB2 and ErbB2 ectodomain complex was constructed by computer-aided molecular modeling. The binding site on ErbB2 ectodomain for herstatin was determined at S1 domain. The mutants of ErbB2 ectodomain were constructed. The interactions of ErbB2 ectodomain and its mutants with herstatin were analyzed for the first time in living cells that coexpressed herstatin and ErbB2 ectodomain or the mutants. The S1 domain in ErbB2 ectodomain was verified as the interaction site with herstatin by immunoprecipitation, confocal microscopy, and fluorescence resonance energy transfer (FRET). The binding region of herstatin on ErbB2 ectodomain might be a potential target region for the drug design.
机译:直接干预转变ErbB2的潜力已成为一个伟大的主题的兴趣。的相互作用可能导致新的治疗方法治疗各种肿瘤。ErbB受体可以抑制信号合理设计肽模拟的基础上子域的ErbB ectodomain。绑定到ErbB受体特别块inter-receptor交互,导致的ErbB2-overexpressing细胞的生长抑制体外。herstatin结构,ErbB2的autoinhibitor和ErbB2 ectodomain复杂的构造了计算机辅助分子建模。网站ErbB2 ectodomain herstatin是决定在S1域。ectodomain构造。与herstatin ErbB2 ectodomain及其突变体在活细胞首次分析了吗, coexpressed herstatin和ErbB2 ectodomain或突变体。被验证为互动网站herstatin通过免疫沉淀反应,共焦显微镜,荧光共振能量转移(烦恼)。在ErbB2 ectodomain可能是一个潜在的目标药物设计的地区。

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