STRUCTURE OF PESTIVIRUS ENVELOPE PROTEINS

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。 这个项目的总体目标是了解害虫病毒家族的成员是如何组装的，以及他们如何进入宿主细胞。我们专注于包膜病毒进入细胞的关键步骤：病毒和宿主细胞膜的融合。膜融合是包膜病毒进入细胞的关键步骤，因为它将病毒基因组送入细胞质。我们以前已经确定了几个相关黄病毒家族的包膜蛋白融合前和融合后的结构。这些结构为这些病毒的膜融合机制提供了重要的见解。然而，黄病毒和鼠疫病毒的囊膜蛋白有很大的差异，并且鼠疫病毒的囊膜蛋白有望采用新的蛋白折叠。膜融合的机制也可能在显著方面有所不同。目前没有任何鼠疫病毒结构蛋白的结构信息(只有所谓的非结构蛋白的结构可用)。为了更好地了解鼠疫病毒的组装和细胞进入，我们建议确定三种不同的肝炎病毒包膜蛋白的结构。我们对鼠疫病毒包膜蛋白的结构将促进我们对鼠疫病毒组装和细胞进入的理解。害虫病毒对牲畜造成严重损害，并与丙型肝炎病毒等人类重要病原体有关。我们的工作将首次提供对构成鼠疫病毒外层蛋白外壳的蛋白质的结构洞察。对这个外层蛋白质外壳的直接观察对于了解瘟疫病毒如何组装它们的蛋白质外壳是至关重要的，并将揭示暴露在病毒表面的蛋白质表位的确切性质和范围。这将为抗病毒化合物的合理设计提供一个框架，使其与病毒膜融合或病毒附着在细胞上。

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. The overall goal of this project is to understand how members of the Pestivirus family assemble, and how they enter the host cell. We focus on a key step in the entry of enveloped viruses into the cell: fusion of the viral and host cell membranes. Membrane fusion is an essential step in entry of enveloped viruses because it delivers the viral genome into the cytoplasm. We have previously determined the pre- and postfusion structures of the postfusion of several envelope proteins from the related flavivirus family. These structures yielded important insights into the membrane fusion mechanism of these viruses. However, flaviviruses and pestiviruses have substantially divergent envelope proteins, and the pestivirus envelope proteins are expected to adopt novel protein folds. The mechanism of membrane fusion may also differ in significant ways. There is currently no structural information of any pestivirus structural protein (only structure of the so-called non-structural proteins are available). In order to gain a better understanding of pestivirus assembly and cell entry, we propose to determine the structure of three different hepacivirus envelope proteins. Our structures of pestivirus envelope proteins will advance our understanding of pestivirus assembly and cell entry. Pestiviruses cause serious damage to livestock and are related to important human pathogens such as Hepatitis C virus. Our work will provide the first structural insight into the proteins that form the outer protein shell of pestiviruses. A direct view of this outer protein shell is essential for understanding how pestiviruses assemble their protein coats, and will reveal the precise nature and extent of the protein epitopes that are exposed on the viral surface. This will provide a framework for the rational design of antiviral compounds that viral membrane fusion, or viral attachment to the cell.