HIV PROTEINS AND PROTEIN INTERACTIONS

HIV 蛋白质和蛋白质相互作用

• 批准号: 8363832
• 负责人: Robert M Stroud
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363832
• 关键词: Complex; Cytoplasmic Tail; Degradation Pathway; Down-Regulation; Endoplasmic Reticulum; Environment; Funding; Goals; Grant; HIV; HIV-1; Host Defense Mechanism; Human; Infection; Mass Spectrum Analysis; National Center for Research Resources; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Source; Ubiquitin; Ubiquitination; United States National Institutes of Health; base; cost; multicatalytic endopeptidase complex; protein protein interaction; three dimensional structure; ubiquitin ligase; vpu Protein

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HIV encodes for only 15 proteins, but hijacks the use of several human proteins. HIV accessory proteins (Vpu, Vpr, Vif and Nef) form an extensive network of interaction with the human proteins. These interactions allow HIV to manipulate the host cellular environment in a manner that facilitate infection and replication of HIV and downregulation of host defense mechanisms. One of the primary targets for manipulation by HIV is the host ubiquitin-proteasome degradation pathway. HIV-1 Vpu interacts with the multi-subunit Cul1-Roc1-Skp1-bTrCP ubiquitin-ligase complex or the SCF complex and promotes the degradation of CD4 in the endoplasmic reticulum. Vpu forms a ternary complex with the cytoplasmic tail of CD4 and bTrCP, which promotes the ubiquitination and subsequent degradation of CD4. The goal of this project is to determine: a) the structural basis of recognition of Vpu by bTrCP; b) the structural basis of the interaction between CD4 and Vpu; c) the three-dimensional structure of the bTrCP-Vpu-CD4 ternary complex. Mass Spectroscopy analysis will facilitate characterization of protein interaction and identification purified proteins.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 艾滋病毒只编码15种蛋白质，但劫持了几种人类蛋白质的使用。 HIV辅助蛋白（Vpu、Vpr、Vif和Nef）与人类蛋白质形成广泛的相互作用网络。 这些相互作用使HIV能够以促进HIV感染和复制以及下调宿主防御机制的方式操纵宿主细胞环境。 HIV操纵的主要靶标之一是宿主泛素-蛋白酶体降解途径。 HIV-1 Vpu与多亚基Cul 1-Roc 1-Skp 1-bTrCP泛素连接酶复合物或SCF复合物相互作用，促进内质网中CD 4的降解。 Vpu与CD 4的胞质尾区和bTrCP形成三元复合物，其促进CD 4的泛素化和随后的降解。 本项目的目标是确定：a）bTrCP识别Vpu的结构基础; B）CD 4与Vpu相互作用的结构基础; c）bTrCP-Vpu-CD 4三元复合物的三维结构。 质谱分析将有助于表征蛋白质相互作用和鉴定纯化的蛋白质。