阻断乙型肝炎病毒组装的肽：通过冷冻显微镜、诱变和转染进行分析
Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection.
作者信息
Böttcher B, Tsuji N, Takahashi H, Dyson M R, Zhao S, Crowther R A, Murray K
机构信息
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
出版信息
EMBO J. 1998 Dec 1;17(23):6839-45. doi: 10.1093/emboj/17.23.6839.
Abstract
Peptides selected to bind to hepatitis B virus (HBV) core protein block interaction with the long viral surface antigen (L-HBsAg) in vitro. High resolution electron cryomicroscopy showed that one such peptide binds at the tips of the spikes of the core protein shell. The peptides contain two basic residues; changing either of two acidic residues at the spike tip to an alanine greatly reduced the binding affinity. Transfection of hepatoma cells with a replication-competent HBV plasmid gave significantly reduced production of virus in the presence of peptide, in a dose-dependent manner. These experiments show that the interaction of L-HBsAg with core particles is critical for HBV assembly, and give proof of principle for its disruption in vivo by small molecules.
摘要
被选择与乙型肝炎病毒（HBV）核心蛋白结合的肽在体外可阻断其与长病毒表面抗原（L-HBsAg）的相互作用。高分辨率冷冻电子显微镜显示，其中一种肽结合在核心蛋白壳的刺突尖端。这些肽含有两个碱性残基；将刺突尖端的两个酸性残基中的任何一个替换为丙氨酸都会大大降低结合亲和力。用具有复制能力的HBV质粒转染肝癌细胞后，在存在肽的情况下，病毒产生量会以剂量依赖的方式显著降低。这些实验表明，L-HBsAg与核心颗粒的相互作用对HBV组装至关重要，并为小分子在体内破坏这种相互作用提供了原理证明。
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