Epitopes described in "Structural elucidation of critical residues involved in binding of human monoclonal antibodies to hepatitis C virus E2 envelope glycoprotein."

Reference
Article Authors:Roxana E Iacob; Zhenyong Keck; Oakley Olson; Steven K H Foung; Kenneth B Tomer
Article Title:Structural elucidation of critical residues involved in binding of human monoclonal antibodies to hepatitis C virus E2 envelope glycoprotein.
Reference Detail
Reference ID:1007934
Abstract:Human monoclonal antibodies derived from B cells of HCV-infected individuals provide information on the immune response to native HCV envelope proteins as they are recognized during infection. Monoclonal antibodies have been useful in the determination of the function and structure of specific immunogenic domains of proteins and should also be useful for the structure/function characterization of HCV E1 and E2 envelope glycoproteins. The HCV E2 envelope glycoprotein has at least three immunodistinctive conformation domains, designated A, B, and C. Conformational epitopes within domain B and C are neutralizing antibody targets on HCV pseudoparticles as well as from infectious cell culture virus. In this study, a combination of differential surface modification and mass spectrometric limited proteolysis followed by alanine mutagenesis was used to provide insight into potential conformational changes within the E2 protein upon antibody binding. The arginine guanidine groups in the E2 protein were modified with CHD in both the affinity bound and free states followed by mass spectrometric analysis, and the regions showing protection upon antibody binding were identified. This protection can arise by direct contact between the residues and the monoclonal antibody, or by antibody-induced conformational changes. Based on the mass spectrometric data, site-directed mutagenesis experiments were performed which clearly identified additional amino acid residues on E2 distant from the site of antibody interaction, whose change to alanine inhibited antibody recognition by inducing conformational changes within the E2 protein.
Date:2008
Reference Type:Literature
PubMed ID:18230369
Journal:Biochim Biophys Acta
Journal Volume:1784
Article Pages:530-42
Journal ISSN:0006-3002
Article Chemical List:Antibodies, Monoclonal;Antigen-Antibody Complex;Hepatitis C Antibodies;Immunodominant Epitopes;Viral Envelope Proteins;glycoprotein E2, Hepatitis C virus;Arginine
Article MeSH List:Amino Acid Sequence; Antibodies, Monoclonal(immunology); Antigen-Antibody Complex(chemistry; immunology); Antigen-Antibody Reactions; Arginine(chemistry; genetics); Epitope Mapping; Hepatitis C Antibodies(immunology); Humans; Immunodominant Epitopes(chemistry; genetics; immunology); Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Conformation; Viral Envelope Proteins(chemistry; genetics; immunology)
Curation Last Updated:2014-04-01 18:58:07