HEPATITUS C P7 VIROPORIN

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 丙型肝炎病毒（HCV）感染是一个重大的全球健康问题，也是一个主要的问题 慢性肝炎、肝硬化和肝细胞癌的病因。所述hcv p7蛋白是一种63个氨基酸的小的整合膜蛋白， 并形成阳离子选择性孔。最近的研究表明，P7 离子通道活性是有效组装和释放新生的 HCV病毒粒子[1]。没有p7的晶体结构，然而，基于 实验数据进行了探索。p7单体形成两个反平行的 由保守的胞质带电环区连接的跨膜片段， 其N-和C-末端均面向内质网腔[2]。 已经观察到p7寡聚体的七聚体和六聚体形式[3，4，5]， 以及基于二级结构的p7复合体的几种假设模型 预测已经报道[6，3，5，7]。最近，一个低分辨率的低温- Luik等人的短尾脂质环境（DHPC）中p7的EM图谱显示， 花状六聚体结构[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].