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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 HIV 仅编码 15 种蛋白质，但却劫持了多种人类蛋白质的使用。 HIV 辅助蛋白（Vpu、Vpr、Vif 和 Nef）与人类蛋白形成广泛的相互作用网络。 这些相互作用使得HIV能够以促进HIV感染和复制以及宿主防御机制下调的方式操纵宿主细胞环境。 HIV 操纵的主要目标之一是宿主泛素-蛋白酶体降解途径。 HIV-1 Vpu 与多亚基 Cul1-Roc1-Skp1-bTrCP 泛素连接酶复合物或 SCF 复合物相互作用，促进内质网中 CD4 的降解。 Vpu与CD4和bTrCP的胞质尾部形成三元复合物，促进CD4的泛素化和随后的降解。 该项目的目标是确定： a) bTrCP 识别 Vpu 的结构基础； b) CD4和Vpu相互作用的结构基础； c) bTrCP-Vpu-CD4三元复合物的三维结构。 质谱分析将有助于蛋白质相互作用的表征和纯化蛋白质的鉴定。