HEPATITUS C P7 VIROPORIN

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 丙型肝炎病毒(丙型肝炎病毒)感染是一个重大的全球健康问题，也是 慢性肝炎、肝硬变和肝细胞癌的病因。丙型肝炎病毒 P7蛋白是一种由63个氨基酸组成的小分子膜蛋白，由63个氨基酸组成 并形成阳离子选择性孔道。最近已经证明，p7 离子通道活动是有效组装和释放新生细胞所必需的 丙型肝炎病毒粒子[1]。然而，没有p7的晶体结构，基于 对实验数据进行了探索。P7单体形成两个反平行 由保守的胞质带电环区连接的跨膜片段， N-末端和C-末端都面向内质网腔[2]。 观察到P7齐聚物以七聚体和六聚体形式[3，4，5]， 以及基于二级结构的P7复合体的几种假想模型 已经报道了预测[6，3，5，7]。最近，一台低分辨率的低温- Luik等人在短尾脂质环境(DHPC)中p7的EM图。透露出一种 花状六面体结构[5]。

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. Hepatitis C virus (HCV) infection is a major, global health problem and a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The HCV p7 protein is a small integral membrane protein of 63 amino acids which oligomerizes and forms cation-selective pores. It has recently been demonstrated that p7 ion channel activity is required for the effective assembly and release of nascent HCV virions [1]. There is no crystal structure of p7, however, models based on experimental data have been explored. The p7 monomer forms two antiparallel transmembrane segments connected by a conserved cytosolic charged loop region, with both the N- and C-termini facing the lumen of the endoplasmic reticulum [2]. p7 oligomers have been observed in both heptameric and hexameric forms [3, 4, 5], and several hypothetical models of the p7 complex based on secondary-structure predictions have been reported [6, 3, 5, 7]. Most recently, a low-resolution cryo- EM map of p7 in a short-tail lipid environment (DHPC) by Luik et al. revealed a flower-like hexameric structure [5].