title: Hepatitis C virus E2 envelope glycoprotein core structure.
abstract: 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.
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Leopold
authors.initials: L
authors.lastname: Kong
authors.forename: Erick
authors.initials: E
authors.lastname: Giang
authors.forename: Travis
authors.initials: T
authors.lastname: Nieusma
authors.forename: Rameshwar U
authors.initials: RU
authors.lastname: Kadam
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Cogburn
authors.forename: Yuanzi
authors.initials: Y
authors.lastname: Hua
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Dai
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Stanfield
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Mansun
authors.initials: M
authors.lastname: Law
mesh_terms: D057134:Antibodies, Neutralizing / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D060225:Tetraspanin 28 / Q000737:chemistry; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000737:chemistry / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; C554798:CD81 protein, human; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C091015:glycoprotein E2, Hepatitis C virus