Role of Vpu in HIV1 Particle Exit

描述（由申请人提供）：本提案侧重于以下方面的作用： 病毒颗粒出口中的病毒蛋白U（Vpu）。我们的长期目标是 一个全面的图片，描述了艾滋病毒颗粒的分子机制 以及Vpu在这个过程中所扮演的角色。我们的实验是 围绕着Vpu和一种新的细胞蛋白质之间的相互作用 命名为Vpu结合蛋白（Ubp）。这种新的细胞蛋白是一种 一个蛋白质超家族，包含重复拷贝的基序，称为 TPR基序，促进特异性蛋白质-蛋白质相互作用。我们 初步数据还表明Ubp与Gag特异性相互作用。这 可能是重要的，因为Vpu的最终间接目标可能是 成为加格的一员初步数据显示，正常 Ubp的功能是调节多蛋白伴侣复合物， 与Hsp 70的C-末端调节结构域相互作用。有几 这一建议的补充目标。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-蛋白质相互作用的作用 关联在Vpu介导的颗粒退出中起作用。此外，我们将扩大 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 Ubp-Gag相互作用。在第二个表面上独立的生物活动中， Vpu促进CD 4的降解。一些拟议的实验将 确定Ubp是否在Vpu活性中起作用。另外的遗传 将进行实验，以确定第二个网站的性质 回复突变体是在初级Vpu突变体繁殖后产生的。

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.