Structural basis of the interactions between tyrosine kinase c-Src and the Hepatitis C virus proteins NS5A and NS5B, and their influence on liver damage and regeneration (A11)

酪氨酸激酶 c-Src 与丙型肝炎病毒蛋白 NS5A 和 NS5B 相互作用的结构基础及其对肝损伤和再生的影响 (A11)

• 批准号: 211900535
• 金额: --
• 依托单位: Institut für Physikalische Biologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/211900535?language=en
• 关键词: Structural; basis; interactions; between; tyrosine

In HCV infected cells tyrosine kinase c-Src, which is important for regulation of cell growth and differentiation, is recruited into the viral replication machinery by the HCV proteins NS5A and -B. The intrinsically disordered character and tyrosine-phosphorylation of NS5A seems to be crucial for NS5A/B/ c-Src complex formation. Our results demonstrate canonical SH2- and SH3- as well as non-canonical SH3-binding of NS5A with c-Src, but no direct NS5B/ c-Src interaction. Our focus now lies on the establishment of complex reconstitution in nanodiscs and its structural analysis. Specific inhibitors of complex formation will help to understand how NS5A and -B influence normal c-Src functions.

在HCV感染的细胞中，酪氨酸激酶c-Src对细胞生长和分化的调节很重要，它通过HCV蛋白NS5A和-B被招募到病毒复制机制中。NS5A的内在无序特性和酪氨酸磷酸化似乎对NS5A/B/ c-Src复合物的形成至关重要。我们的研究结果表明NS5A与c-Src有典型的SH2-和SH3-结合，以及非典型的SH3-结合，但没有直接的NS5B/ c-Src相互作用。我们现在的重点是建立纳米片的复杂重构及其结构分析。特异性复合物形成抑制剂将有助于了解NS5A和-B如何影响正常的c-Src功能。