2BDN

Crystal structure of human MCP-1 bound to a blocking antibody, 11K2

2BDN の概要

• エントリーDOI: 10.2210/pdb2bdn/pdb
• 分子名称: Small inducible cytokine A2, Antibody light chain 11K2, Antibody heavy chain 11K2, ... (4 entities in total)
• 機能のキーワード: antibody-antigen complex, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• 細胞内の位置: Secreted : P13500
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 55396.86

構造登録者

Boriack-Sjodin, P.A.,Rushe, M.,Reid, C.,Jarpe, M.,van Vlijmen, H.,Bailly, V. (登録日: 2005-10-20, 公開日: 2006-06-13, 最終更新日: 2024-11-20)

主引用文献

Reid, C.,Rushe, M.,Jarpe, M.,van Vlijmen, H.,Dolinski, B.,Qian, F.,Cachero, T.G.,Cuervo, H.,Yanachkova, M.,Nwankwo, C.,Wang, X.,Etienne, N.,Garber, E.,Bailly, V.,de Fougerolles, A.,Boriack-Sjodin, P.A.
Structure activity relationships of monocyte chemoattractant proteins in complex with a blocking antibody.
Protein Eng.Des.Sel., 19:317-324, 2006

PubMed Abstract: Monocyte chemoattractant proteins (MCPs) are cytokines that direct immune cells bearing appropriate receptors to sites of inflammation or injury and are therefore attractive therapeutic targets for inhibitory molecules. 11K2 is a blocking mouse monoclonal antibody active against several human and murine MCPs. A 2.5 A structure of the Fab fragment of this antibody in complex with human MCP-1 has been solved. The Fab blocks CCR2 receptor binding to MCP-1 through an adjacent but distinct binding site. The orientation of the Fab indicates that a single MCP-1 dimer will bind two 11K2 antibodies. Several key residues on the antibody and on human MCPs were predicted to be involved in antibody selectivity. Mutational analysis of these residues confirms their involvement in the antibody-chemokine interaction. In addition to mutations that decreased or disrupted binding, one antibody mutation resulted in a 70-fold increase in affinity for human MCP-2. A key residue missing in human MCP-3, a chemokine not recognized by the antibody, was identified and engineering the preferred residue into the chemokine conferred binding to the antibody.

PubMed: 16682434
DOI: 10.1093/protein/gzl015

実験手法

X-RAY DIFFRACTION (2.53 Å)