Structural Studies of Alix and ESCRT Complexes in HIV-1 Budding

HIV-1出芽过程中阿利克斯和ESCRT复合物的结构研究 HIV-1颗粒的组装和释放依赖于一个蛋白质网络，包括阿利克斯和Vps 4A/B，以及四种多蛋白复合物：Hrs/STAM和ESCRT-I、II和III。这些蛋白质和复合物从酵母到人类都是保守的，它们的正常功能是将单泛素化受体、酶和其他货物分类到溶酶体或液泡。在这个网络中测试的几种蛋白质中的任何一种失活都会阻止HIV的释放和感染性。在过去的努力，在这个项目中，我们映射的HIV和ESCRT组件之间的分子相互作用在单个蛋白质结构域的水平和特征的结合亲和力和相关结构的组件参与这些相互作用。展望未来，该项目的目标将是在体外重建HIV-1的组装和ESCRT介导的出芽，并与NCI的Eric Freed合作，设计抑制HIV-1从细胞出芽的方法。

Structural Studies of Alix and ESCRT Complexes in HIV-1 Budding HIV-1 particle assembly and release depend on a protein network that includes Alix and Vps4A/B, and four multiprotein complexes: Hrs/STAM and ESCRT-I, II, and III. These proteins and complexes are conserved from yeast to human, and their normal function is to sort monoubiquitinated receptors, enzymes, and other cargo to the lysosome or vacuole. Inactivation of any one of several proteins tested in this network blocks HIV release and infectivity. In past effort in this project, we mapped the molecular interactions between HIV and ESCRT components at the level of individual protein domains and characterized the binding affinities and relevant structures of the components involved in these interactions. Looking ahead, the goals of this project will be to reconstitute the assembly and ESCRT-mediated budding of HIV-1 in vitro, and, in collaboration with Eric Freed, NCI, to design means for inhibiting HIV-1 budding from cells.