title: Discrete conformations of epitope II on the hepatitis C virus E2 protein for antibody-mediated neutralization and nonneutralization.
abstract: The X-ray crystal structure of epitope II on the E2 protein of hepatitis C virus, in complex with nonneutralizing antibody mAb#12, has been solved at 2.90-Å resolution. The spatial arrangement of the essential components of epitope II (ie, the C-terminal α-helix and the N-terminal loop) was found to deviate significantly from that observed in those corresponding complexes with neutralizing antibodies. The distinct conformations are mediated largely by the flexibility of a highly conserved glycine residue that connects these components. Thus, it is the particular tertiary structure of epitope II, which is presented in a spatial and temporal manner, that determines the specificity of antibody recognition and, consequently, the outcome of neutralization or nonneutralization.
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892;
authors.forename: Lu
authors.initials: L
authors.lastname: Deng
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892;
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892;
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Virata
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892;
authors.forename: Lilin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892;
authors.forename: Hailing
authors.initials: H
authors.lastname: Yan
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892;
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892;
authors.forename: Evi
authors.initials: E
authors.lastname: Struble
authors.affiliation: Department of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC 20037; and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Feinstone
authors.affiliation: Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 pei.zhang@fda.hhs.gov halter@dtm.cc.nih.gov.
authors.forename: Harvey
authors.initials: H
authors.lastname: Alter
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892; pei.zhang@fda.hhs.gov halter@dtm.cc.nih.gov.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology*; D017124:Conserved Sequence / Q000235:genetics; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry*; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000737:chemistry* / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus
keywords: immunoglobulins; prophylaxis; vaccine