Broadly Neutralizing Anti-hepatitis B Virus Antibody Reveals a Complementarity Determining Region H3 Lid-opening Mechanism.
From: Center for Cellular Switch Protein Structure, Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: May 2007
- ISSN: 0027-8424
- Volume: 104
- Issue: 22
- Pages: 9230-5
- Medium: Print
- Language: English
- Citation (JAMA): Chi Seung-Wook, Maeng Cheol-Young, Kim Seung Jun, et al. Broadly Neutralizing Anti-hepatitis B Virus Antibody Reveals a Complementarity Determining Region H3 Lid-opening Mechanism.. Proc. Natl. Acad. Sci. U.S.A. May 2007;104:9230-5
Abstract
The humanized monoclonal antibody HzKR127 recognizes the preS1 domain of the human hepatitis B virus surface proteins with a broadly neutralizing activity in vivo. We present the crystal structures of HzKR127 Fab and its complex with a major epitope peptide. In the complex structure, the bound peptide forms a type IV beta-turn followed by 3(10) helical turn, the looped-out conformation of which provides a structural basis for broad neutralization. Upon peptide binding, the antibody undergoes a dramatic complementarity determining region H3 lid opening. To understand the structural implication of the virus neutralization, we carried out comprehensive alanine-scanning mutagenesis of all complementarity determining region residues in HzKR127 Fab. The functional mapping of the antigen-combining site demonstrates the specific roles of major binding determinants in antigen binding, contributing to the rational design for maximal humanization and affinity maturation of the antibody.
Mesh Headings (Keywords): Amino Acid Sequence, Antigens, Binding Sites, Complementarity Determining Regions, Crystallography, X-Ray, Hepatitis B Antibodies, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Peptides, Protein Structure, Quaternary, Sensitivity and Specificity, Viral Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 17517649
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