STRUCTURAL STUDIES OF VPU IN PHOSPHOLIPID MONOLAYERS AND BILAYERS

我们计划研究HIV-1辅助蛋白的结构 矢量定向单膜系统内的Vpu 最先进的同步辐射X射线散射和冷 中子散射技术 二级和四级 Vpu跨膜结构域的结构，包括 钾阳离子在这个领域，和三级结构的 Vpu的胞质结构域，包括后者对 其Ser 52和Ser 56残基的磷酸化，将是特别重要的。 兴趣 由于跨膜结构域及其相关的 单价阳离子通道活性负责增强病毒 从细胞表面释放，其胞质结构域负责 对于磷酸化依赖性诱导的降解， HIV受体CD$的结构研究，预计将 提供了大量的洞察机制的Vpu的两个 HIV-1感染过程中涉及的独立行动。 在 此外，通过如此确定跨膜的结构起源， 结构域的通道活性，药物干预的潜在靶点 基于Vpu特异性通道阻滞剂的发展， 提供了

Well plan to investigate the structure of the HIV-1 accessory protein Vpu within vectorially-oriented single membrane systems utilizing state-of-the-art synchrotron radiation-based x-ray scattering and cold neutron scattering techniques. The secondary and quaternary structures of Vpu's transmembrane domain, including the locations of potassium cations within this domain, and the tertiary structure of Vpu's cytoplasmic domain, including the latter's dependence on the phosphorylation of its of Ser52 and Ser56 residues, will be of particular interest. Since the transmembrane domain and its associated monovalent cation channel activity are responsible for enhancing virus release from the cell surface and its cytoplasmic domain is responsible for the phosphorylation-dependent induction of degradation of the HIV receptor CD$, the structural studies proposed are expected to provide substantial insight into the mechanism of Vpu's two independent actions involved in the course of HIV-1 infection. In addition, by so-determining the structural origin of the transmembrane domain's channel activity, a potential target for drug intervention based on the development of Vpu-specific channel blockers would be provided.