5WK3

CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN CCL17 AND M116 FAB

5WK3 の概要

• エントリーDOI: 10.2210/pdb5wk3/pdb
• 分子名称: M116 LIGHT CHAIN, M116 HEAVY CHAIN, C-C motif chemokine 17, ... (5 entities in total)
• 機能のキーワード: immune system
• 由来する生物種: Homo sapiens (HUMAN); 詳細
• 細胞内の位置: Secreted: Q92583
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 228023.15

構造登録者

Teplyakov, A.,Obmolova, G.,Gilliland, G.L. (登録日: 2017-07-24, 公開日: 2017-12-20, 最終更新日: 2024-11-13)

主引用文献

Teplyakov, A.,Obmolova, G.,Gilliland, G.L.
Structural insights into chemokine CCL17 recognition by antibody M116.
Biochem Biophys Rep, 13:27-31, 2018

PubMed Abstract: The homeostatic chemokine CCL17, also known as thymus and activation regulated chemokine (TARC), has been associated with various diseases such as asthma, idiopathic pulmonary fibrosis, atopic dermatitis and ulcerative colitis. Neutralization of CCL17 by antibody treatment ameliorates the impact of disease by blocking influx of T cells. Monoclonal antibody M116 derived from a combinatorial library shows potency in neutralizing CCL17-induced signaling. To gain insight into the structural determinants of antigen recognition, the crystal structure of M116 Fab was determined in complex with CCL17 and in the unbound form. Comparison of the structures revealed an unusual induced-fit mechanism of antigen recognition that involves isomerization in two CDRs. The structure of the CCL17-M116 complex revealed the antibody binding epitope, which does not overlap with the putative receptor epitope, suggesting that the current model of chemokine-receptor interactions, as observed in the CXCR4-vMIP-II system, may not be universal.

PubMed: 29264403
DOI: 10.1016/j.bbrep.2017.11.005

実験手法

X-RAY DIFFRACTION (1.9 Å)