Structural evidence for a bifurcated mode of action in the antibody-mediated neutralization of hepatitis C virus.

Abstract

Hepatitis C virus (HCV) envelope glycoprotein E2 has been considered as a major target for vaccine design. Epitope II, mapped between residues 427-446 within the E2 protein, elicits antibodies that are either neutralizing or nonneutralizing. The fundamental mechanism of antibody-mediated neutralization at epitope II remains to be defined at the atomic level. Here we report the crystal structure of the epitope II peptide in complex with a monoclonal antibody (mAb#8) capable of neutralizing HCV. The complex structure revealed that this neutralizing antibody engages epitope II via interactions with both the C-terminal α-helix and the N-terminal loop using a bifurcated mode of action. Our structural insights into the key determinants for the antibody-mediated neutralization may contribute to the immune prophylaxis of HCV infection and the development of an effective HCV vaccine.

• Authors: Lu Deng, Lilin Zhong, Evi Struble, Hongying Duan, Li Ma, Christine Harman, Hailing Yan, Maria Luisa Virata, Zhong Zhao, Stephen Feinstone, Harvey Alter, Pei Zhang
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 110 Issue 18 Pg. 7418-22 (04 30 2013) ISSN: 1091-6490 [Electronic] United States
• PMID: 23589879 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Epitopes
• Hepatitis C Antibodies
• Mutant Proteins
• Peptides

Topics

• Amino Acid Sequence
• Antibodies, Monoclonal (chemistry, immunology)
• Antibodies, Neutralizing (chemistry, immunology)
• Crystallography, X-Ray
• Enzyme-Linked Immunosorbent Assay
• Epitopes (chemistry, immunology)
• Hepacivirus (immunology)
• Hepatitis C Antibodies (chemistry, immunology)
• Molecular Sequence Data
• Mutant Proteins (chemistry)
• Neutralization Tests
• Peptides (chemistry, genetics, immunology)
• Protein Binding (immunology)
• Protein Structure, Secondary
• Static Electricity