Role of Vpu in HIV1 Particle Exit

描述(由申请人提供)：本建议书侧重于 病毒颗粒中的病毒蛋白U(VPU)。我们的长期目标是创造 一张描述HIV颗粒分子机制的综合图片 以及VPU在这一过程中所起的作用。我们的实验是 以VPU和一种新的细胞蛋白之间的相互作用为中心 指定的VPU结合蛋白(UBP)。这种新的细胞蛋白是一个成员 包含一个基序的重复拷贝的蛋白质超家族，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具有特异性相互作用。这 可能意义重大，因为VPU的最终间接目标很可能 成为恶作剧的一部分。额外的初步数据表明，正常的 UBP的功能是通过以下途径调节多蛋白伴侣复合体 与Hsp70的C-末端调节域相互作用。有几个 这项提案的互补目标。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 缔合作用在VPU介导的粒子退出中起作用。此外，我们还将延长 我们的观察表明，UBP调节蛋白质折叠和 确定这种活性与VPU介导的颗粒释放的关系 和UBP-GAG相互作用。在第二个表面上分离的生物活动中， VPU促进了CD4的降解。一些拟议的实验将 确定UBP是否在VPU活动中发挥作用。其他遗传基因 将进行实验以确定第二个地点的性质 随着初级VPU突变体的繁殖而产生的回复突变体。

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.