...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Structure >Solution Structure Analysis of the HPV16 E6 Oncoprotein Reveals a Self-Association Mechanism Required for E6-Mediated Degradation of p53
【24h】

Solution Structure Analysis of the HPV16 E6 Oncoprotein Reveals a Self-Association Mechanism Required for E6-Mediated Degradation of p53

机译：HPV16 E6癌蛋白的溶液结构分析揭示了E6介导的p53降解所需的自缔合机制

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The viral oncoprotein E6 is an essential factor for cervical cancers induced by "high-risk" mucosal HPV. Among other oncogenic activities, E6 recruits the ubiquitin ligase E6AP to promote the ubiquitination and subsequent proteasomal degradation of p53. E6 is prone to self-association, which long precluded its structural analysis. Here we found that E6 specifically dimerizes through its N-terminal domain and that disruption of the dimer interface strongly increases E6 solubility. This allowed us to raise structural data covering the entire HPV16 E6 protein, including the high-resolution NMR structures of the two zinc-binding domains of E6 and a robust data-driven model structure of the N-terminal domain homodimer. Interestingly, homodimer interfacemutations that disrupt E6 self-association also inactivate E6-mediated p53 degradation. These data suggest that E6 needs to self-associate via its N-terminal domain to promote the polyubiquitination of p53 by E6AP.
机译：病毒癌蛋白E6是由“高危”粘膜HPV诱发的宫颈癌的重要因素。在其他致癌活动中，E6募集泛素连接酶E6AP来促进p53的泛素化和随后的蛋白酶体降解。 E6易于自我联想，长期以来一直对其结构分析不利。在这里，我们发现E6通过其N末端结构域特异性二聚，并且二聚体界面的破坏强烈增加了E6的溶解度。这使我们能够提出涵盖整个HPV16 E6蛋白的结构数据，包括E6的两个锌结合域的高分辨率NMR结构以及N端域同二聚体的稳健的数据驱动模型结构。有趣的是，破坏E6自缔合的同型二聚体界面突变也会使E6介导的p53降解失活。这些数据表明E6需要通过其N末端结构域自缔合以促进E6AP对p53的多聚泛素化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号