丙型肝炎病毒 E1E2 糖蛋白复合物的结构。
Structure of the hepatitis C virus E1E2 glycoprotein complex.
机构信息
Department of Integrative Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
出版信息
Science. 2022 Oct 21;378(6617):263-269. doi: 10.1126/science.abn9884. Epub 2022 Oct 20.
Abstract
Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in humans and afflicts more than 58 million people worldwide. The HCV envelope E1 and E2 glycoproteins are essential for viral entry and comprise the primary antigenic target for neutralizing antibody responses. The molecular mechanisms of E1E2 assembly, as well as how the E1E2 heterodimer binds broadly neutralizing antibodies, remain elusive. Here, we present the cryo-electron microscopy structure of the membrane-extracted full-length E1E2 heterodimer in complex with three broadly neutralizing antibodies-AR4A, AT1209, and IGH505-at ~3.5-angstrom resolution. We resolve the interface between the E1 and E2 ectodomains and deliver a blueprint for the rational design of vaccine immunogens and antiviral drugs.
摘要
丙型肝炎病毒（HCV）感染是导致人类慢性肝病、肝硬化和肝细胞癌的主要原因，在全球范围内影响着超过 5800 万人。HCV 包膜 E1 和 E2 糖蛋白是病毒进入所必需的，也是中和抗体反应的主要抗原靶标。E1E2 组装的分子机制，以及 E1E2 异二聚体如何结合广泛中和抗体，仍然难以捉摸。在这里，我们呈现了膜提取全长 E1E2 异二聚体与三种广泛中和抗体（AR4A、AT1209 和 IGH505）在~3.5-埃分辨率下复合物的冷冻电镜结构。我们解析了 E1 和 E2 外域之间的界面，并为疫苗免疫原和抗病毒药物的合理设计提供了蓝图。
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