...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>AIDS Research and Human Retroviruses >Identification of a novel binding site between HIV type 1 nef c-terminal flexible loop and AP2 required for nef-mediated CD4 downregulation
【24h】

Identification of a novel binding site between HIV type 1 nef c-terminal flexible loop and AP2 required for nef-mediated CD4 downregulation

机译：鉴定nef介导的CD4下调所需的HIV 1型nef c末端柔性环与AP2之间的新型结合位点

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

HIV-1 Nef is an accessory protein necessary for HIV-1 virulence and rapid AIDS development. Nef promotes viral replication and infection by connecting CD4 and several other cell surface receptors to the clathrin adaptor protein AP2, resulting in the internalization and degradation of the receptors interacting with Nef. We investigated how Nef can mediate constitutive receptor endocytosis through the interaction of the dileucine motif in its C-terminal flexible loop (C-loop) with AP2, whereas AP2 binding of the transmembrane receptors usually results in an equilibrated (recycled) endocytosis. Our results indicated that in addition to the dileucine motif, there is a second motif in the Nef C-loop involved in the Nef-AP2 interaction. Nef-mediated CD4 downregulation was impaired when the residue in the hydrophobic region in the Nef C-loop (LL 165HPMSLHGM173) was mutated to a basic residue K/R or an acidic residue E/D or to the rigid residue P, or when M168L 170, L170H171, or G172M 173 was mutated to AA. A pull-down assay indicated that AP2 was not coprecipitated with Nef mutants that did not downregulate CD4. Molecular modeling of the Nef C-terminal flexible loop in complex with AP2 suggests that M168L170 occupies a pocket in the AP2 σ2 subunit. Our data suggest a new model in the Nef-AP2 interaction in which the hydrophobic region in the Nef C-loop with the dileucine (L164L165) motif and M168L170 motif binds to AP2(σ2), while the acidic motif E174 and D175 binds to AP2(α), which explains how Nef through the flexible loop connects CD4 to AP2 for constitutive CD4 downregulation.
机译：HIV-1 Nef是HIV-1毒力和艾滋病快速发展所必需的辅助蛋白。 Nef通过将CD4和其他几种细胞表面受体连接到网格蛋白衔接蛋白AP2上来促进病毒复制和感染，从而导致与Nef相互作用的受体的内在化和降解。我们研究了Nef如何通过其C末端柔性环（C环）中的双亮氨酸基序与AP2相互作用来介导组成型受体的内吞作用，而跨膜受体的AP2结合通常导致平衡的（再循环）内吞作用。我们的结果表明，除了双亮氨酸基序以外，Nef C-环中还存在另一个与Nef-AP2相互作用有关的基序。当Nef C环疏水区域（LL 165HPMSLHGM173）突变为碱性残基K / R或酸性残基E / D或刚性残基P或M168L时，Nef介导的CD4下调会受到损害。 170，L170H171或G172M 173突变为AA。下拉测定法表明，AP2未与不下调CD4的Nef突变体共沉淀。与AP2结合的Nef C末端柔性环的分子模型表明，M168L170在AP2σ2亚基中占据一个口袋。我们的数据提示了Nef-AP2相互作用的新模型，其中带有双亮氨酸（L164L165）和M168L170主题的Nef C环中的疏水区域与AP2（σ2）结合，而酸性主题E174和D175与AP2结合（α）解释了Nef如何通过柔性环路将CD4连接到AP2，以进行CD4的下调。

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