Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

Journal Article · Tue Aug 26 00:00:00 EDT 2014 · Science

DOI:https://doi.org/10.1126/science.1243876· OSTI ID:1154700

Kong, Leopold ^[1]; Giang, Erick ^[1]; Nieusma, Travis ^[1]; Kadam, Rameshwar U. ^[1]; Cogburn, Kristin E. ^[1]; Hua, Yuanzi ^[1]; Dai, Xiaoping ^[1]; Stanfield, Robyn L. ^[1]; Burton, Dennis R. ^[1]; Ward, Andrew B. ^[1]; Wilson, Ian A. ^[1]; Law, Mansun ^[1]

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1. The Scripps Research Inst., La Jolla, CA (United States)

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 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.

• Research Organization: SLAC National Accelerator Lab., Menlo Park, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC)
• DOE Contract Number: AC02-76SF00515
• OSTI ID: 1154700
• Report Number(s): SLAC-REPRINT-2014-279
• Journal Information: Science, Vol. 342, Issue 6162; ISSN 0036-8075
• Country of Publication: United States
• Language: English

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