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

HIV-1 出芽中 Alix 和 ESCRT 复合物的结构研究

• 批准号: 7734079
• 负责人: James Hurley
• 金额: $ 34.46万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7734079
• 关键词: Affinity; Binding; Cells; Collaborations; Complex; Enzymes; HIV; HIV-1; Human; Individual; Lysosomes; Maps; Multiprotein Complexes; Proteins; Reporting; Sorting - Cell Movement; Structure; System; Tertiary Protein Structure; Testing; Ubiquitin; Vacuole; Yeasts; design; particle; receptor

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. The objectives of this projects are to 1) map the molecular interactions between HIV and ESCRT components at the level of individual protein domains; 2) characterize the binding affinities and relevant structures of the components involved in these interactions; and 3) in collaboration with Eric Freed, NCI, to design means for inhibiting HIV-1 budding from cells. Progress in FY2008 Efforts in 2008 concentrated on extending the structural characterization of the human ESCRT system, as described also under the ubiquitin binding domains project, and extending studies to the Nef-AP-2 adaptor complex system, as described under the adaptors project report.

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。该项目的目标是：1）在单个蛋白质结构域水平上绘制HIV和ESCRT组分之间的分子相互作用; 2）表征这些相互作用中涉及的组分的结合亲和力和相关结构; 3）与NCI的Eric Freed合作，设计抑制HIV-1从细胞中出芽的方法。 2008财政年度进展情况 2008年的工作集中在扩展人ESCRT系统的结构表征，如泛素结合结构域项目所述，并将研究扩展到Nef-AP-2衔接子复合物系统，如衔接子项目报告所述。