Publication Abstract from PubMed
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.
Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity determining region H3 lid-opening mechanism.,Chi SW, Maeng CY, Kim SJ, Oh MS, Ryu CJ, Kim SJ, Han KH, Hong HJ, Ryu SE Proc Natl Acad Sci U S A. 2007 May 29;104(22):9230-5. Epub 2007 May 17. PMID:17517649[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
