Crystal Structure of the Antigen-Binding Fragment of Apoptosis-Inducing Mouse Anti-Human Fas Monoclonal Antibody HFE7A.
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概要
- 論文の詳細を見る
Binding of Fas ligand to Fas induces apoptosis. The Fas-Fas ligand system plays important roles in many biological processes, including the elimination of autoreactive lymphoid cells. The mouse anti-human Fas monoclonal antibody HFE7A (m-HFE7A), which induces apoptosis, has been humanized based on a structure predicted by homology modeling. A version of humanized HFE7A is currently under development for the treatment of autoimmune diseases such as rheumatoid arthritis. For a deeper understanding of the protein engineering aspect of antibody humanization, for which information on the three-dimensional structure is essential, we determined the crystal structure of the m-HFE7A antigen-binding fragment (Fab) by X-ray crystallography at 2.5 Å resolution. The main-chain conformation of the five loops in the six complementarity-determining regions (CDRs) was correctly predicted with root-mean-square deviations of 0.30-1.04 Å based on a comparison of the crystal structure with the predicted structure. The CDRH3 conformation of the crystal structure, which was not classified as one of the canonical structures, was completely different from that of the predicted structure but adopted the conformation which followed the "H3-rules." The results of charge distribution analysis of the antigen-binding site suggest that electrostatic interactions may be important for its binding to Fas.
- 社団法人 日本生化学会の論文
著者
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Ito Shuichiro
Biomedical Research Laboratories Sankyo Co. Ltd.
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HARUYAMA Hideyuki
Biomedical Research Laboratories, Sankyo Co., Ltd.
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TAKAYAMA Tomoko
Biomedical Research Laboratories, Sankyo Co., Ltd.
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Takayama Tomoko
Biomedical Research Laboratories Sankyo Co. Ltd.
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Ohsumi Jun
Biomedical Research Laboratories Sankyo Co. Ltd.
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Hata Tadashi
Biomedical Research Laboratories Sankyo Co. Ltd.
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Hanzawa Hiroyuki
Biomedical Research Laboratories Sankyo Co. Ltd.
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Ichikawa Kimihisa
Biomedical Research Laboratories Sankyo Co. Ltd.
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Serizawa Nobufusa
Biomedical Research Laboratories Sankyo Co. Ltd.
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