Role of Vpu in HIV1 Particle Exit

Vpu 在 HIV1 粒子退出中的作用

• 批准号: 6348355
• 负责人: ANTONITO T PANGANIBAN
• 金额: $ 22.73万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6348355
• 关键词: cytoskeleton; gag protein; heat shock proteins; host organism interaction; human immunodeficiency virus 1; immunoprecipitation; intracellular transport; microorganism culture; molecular chaperones; protein folding; protein protein interaction; protein structure function; protein transport; virus protein; virus replication

DESCRIPTION (provided by the applicant): This proposal focuses on the role of viral protein U (Vpu) in viral particle exit. Our long term goal is to generate a comprehensive picture that describes the molecular mechanism of HIV particle release and the role that Vpu plays in that process. Our experiments are centered around the interaction between Vpu and a novel cellular protein designated Vpu binding protein (Ubp). This novel cellular protein is a member of a protein superfamily that contain repetitive copies of a motif, termed the TPR motif, that facilitates specific protein-protein interaction. Our preliminary data also indicate that Ubp interacts specifically with Gag. This is likely to be significant since the ultimate indirect target of Vpu is likely to be a component of Gag. Additional preliminary data indicates that the normal function of Ubp is to regulate the multiprotein chaperone complex by interacting with the C-terminal regulatory domain of Hsp70. There are several complementary goals of this proposal. We plan to examine in more detail Vpu-Ubp interaction and Ubp-Gag interaction and the role that these protein-protein associations play in Vpu-mediated particle exit. In addition, we will extend our observations which indicate that Ubp regulates protein folding and determine the relationship of this activity to Vpu-mediated particle release and Ubp-Gag interaction. In a second ostensibly separate biological activity, Vpu facilitates the degradation of CD4. Some proposed experiments will determine whether Ubp plays a role in that activity of Vpu. Additional genetic experiments will be carried out to determine the nature of second site revertants that arise following the propagation of primary Vpu mutants.

描述（由申请人提供）：该提案的重点是 病毒颗粒出口处的病毒蛋白U (Vpu)。我们的长期目标是产生 全面描述HIV颗粒的分子机制 发布以及 Vpu 在该过程中扮演的角色。我们的实验是 以 Vpu 和一种新型细胞蛋白之间的相互作用为中心 指定为Vpu结合蛋白(Ubp)。这种新型细胞蛋白是 包含重复拷贝的基序的蛋白质超家族，称为 TPR 基序，促进特定的蛋白质-蛋白质相互作用。我们的 初步数据还表明 Ubp 与 Gag 发生特异性相互作用。这 可能很重要，因为 Vpu 的最终间接目标很可能 成为 Gag 的组成部分。额外的初步数据表明，正常 Ubp 的功能是通过调节多蛋白伴侣复合物 与 Hsp70 的 C 端调控域相互作用。有几个 本提案的补充目标。我们计划更详细地研究 Vpu-Ubp 相互作用和 Ubp-Gag 相互作用以及这些蛋白质-蛋白质的作用 关联在 Vpu 介导的粒子退出中发挥作用。此外，我们还将延长 我们的观察表明 Ubp 调节蛋白质折叠 确定该活性与 Vpu 介导的颗粒释放的关系 和 Ubp-Gag 相互作用。在第二个表面上独立的生物活动中， Vpu 促进 CD4 的降解。一些提议的实验将 确定 Ubp 是否在 Vpu 的活动中发挥作用。额外遗传 将进行实验以确定第二个地点的性质 原代 Vpu 突变体繁殖后出现的回复突变体。