Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity determining region H3 lid-opening mechanism

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Title
Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity determining region H3 lid-opening mechanism
Author(s)
Seung-Wook Chi; C Y Maeng; Seung Jun Kim; M S Oh; C J Ryu; Sang Jick Kim; Kyou Hoon Han; Hyo Jeong Hong; Seong Eon Ryu
Bibliographic Citation
Proceedings of National Academy of Sciences of United States of America, vol. 104, no. 22, pp. 9230-9235
Publication Year
2007
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 β-turn followed by 310 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.
Keyword
Alanine-scanning mutagenesisCrystal structureHumanized antibodyVirus neutralization
ISSN
0027-8424
Publisher
Natl Acad Sciences
DOI
http://dx.doi.org/10.1073/pnas.0701279104
Type
Article
Appears in Collections:
Division of Biomedical Research > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
Synthetic Biology and Bioengineering Research Institute > Synthetic Biology Research Center > 1. Journal Articles
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