3CXD

Crystal structure of anti-osteopontin antibody 23C3 in complex with its epitope peptide

3CXD の概要

• エントリーDOI: 10.2210/pdb3cxd/pdb
• 分子名称: Fab fragment of anti-osteopontin antibody 23C3, Light chain, Fab fragment of anti-osteopontin antibody 23C3, Heavy chain, a peptide from osteopontin, ... (4 entities in total)
• 機能のキーワード: fab, osteopontin, opn, antibody-antigen complex, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Secreted: P10451
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 48307.53

構造登録者

Du, J.,Yang, H.,Zhong, C.,Ding, J. (登録日: 2008-04-24, 公開日: 2008-10-14, 最終更新日: 2024-10-30)

主引用文献

Du, J.,Hou, S.,Zhong, C.,Lai, Z.,Yang, H.,Dai, J.,Zhang, D.,Wang, H.,Guo, Y.,Ding, J.
Molecular basis of recognition of human osteopontin by 23C3, a potential therapeutic antibody for treatment of rheumatoid arthritis
J.Mol.Biol., 382:835-842, 2008

PubMed Abstract: Osteopontin plays an important role in the development and perpetuation of rheumatoid arthritis (RA). Antibodies targeting osteopontin have shown promising therapeutic benefits against this disease. We have previously reported a novel anti-RA monoclonal antibody, namely, 23C3, and shown it capable of alleviating the symptoms of RA in a murine collagen-induced arthritis model, restoring the cytokine production profile in joint tissues, and reducing T-cell recall responses to collagen type II. We describe here the crystal structure of 23C3 in complex with its epitope peptide. Analyses of the complex structure reveal the molecular mechanism of osteopontin recognition by 23C3. The peptide folds into two tandem beta-turns, and two key residues of the peptide are identified to be critical for the recognition by 23C3: TrpP43 is deeply embedded into a hydrophobic pocket formed by AlaL34, TyrL36, LeuL46, TyrL49, PheL91, and MetH102 and therefore has extensive hydrophobic interactions with 23C3, while AspP47 has a network of hydrophilic interactions with residues ArgH50, ArgH52, SerH53, and AsnH56 of the antibody. Besides the complementarity-determining region loops, the framework region L2 of 23C3 is also shown to interact with the epitope peptide, which is not common in the antibody-antigen interactions and thus could be exploited in the engineering of 23C3. These results not only provide valuable information for further improvement of 23C3 such as chimerization or humanization for its therapeutic application, but also reveal the features of this specific epitope of osteopontin that may be useful for the development of new antibody drugs against RA.

PubMed: 18694758
DOI: 10.1016/j.jmb.2008.07.075

実験手法

X-RAY DIFFRACTION (2.8 Å)