Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

See allHide authors and affiliations

Science  29 Nov 2013:
Vol. 342, Issue 6162, pp. 1090-1094
DOI: 10.1126/science.1243876

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Deciphering Hepatitis C

Hepatitis C virus is a major cause of liver disease and cancer. Two envelope glycoproteins, E1 and E2, form a heterodimer that facilitates infection. The envelope proteins have been difficult to crystallize, hindering vaccine development. Kong et al. (p. 1090) designed an E2 core glycoprotein construct and solved the crystal structure of the glycosylated protein in complex with a broadly neutralizing antibody. The host cell receptor binding site was identified by electron microscopy and mutagenesis. The findings should help in future drug and vaccine design.


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.

View Full Text