Hepatitis C virus E2 envelope glycoprotein core structure.

Hepatitis C virus E2 envelope glycoprotein core structure.
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DOI:
10.1126/science.1243876
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发表时间:
2013-11-29
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Law M
Law M
中科院分区:
其他
文献类型:
--
作者:
Kong L;Giang E;Nieusma T;Kadam RU;Cogburn KE;Hua Y;Dai X;Stanfield RL;Burton DR;Ward AB;Wilson IA;Law M

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丙型肝炎病毒(Hepatitis C virus,HCV)是引起病毒性肝炎、肝硬化和肝细胞癌的主要原因。HCV包膜糖蛋白E1和E2介导融合和进入宿主细胞,并且是体液免疫应答的主要靶标。在2.65 nm处与广泛中和抗体AR 3C结合的E2核心的晶体结构显示了由中心Ig折叠β-夹心和两侧的两个额外蛋白层组成的紧凑结构。通过EM和定点诱变鉴定CD 81受体结合位点,并与AR 3C表位重叠。X射线和EM E2结构与扩展的三结构域II类融合蛋白折叠的预测明显不同,因此为HCV药物和疫苗设计提供了宝贵的信息。
Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 Å reveals a compact architecture composed of a central Ig-fold β-sandwich flanked by two additional protein layers. The CD81 receptor-binding site was identified by EM and by site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and EM E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide invaluable information for HCV drug and vaccine design.
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