6KVA

Structure of anti-hCXCR2 abN48-2 in complex with its CXCR2 epitope

6KVA の概要

• エントリーDOI: 10.2210/pdb6kva/pdb
• 分子名称: heavy chain, light chain, Peptide from C-X-C chemokine receptor type 2, ... (5 entities in total)
• 機能のキーワード: antibody-antigen complex, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 98407.56

構造登録者

Xiang, J.C.,Yan, L.,Yang, B.,Wilson, I.A. (登録日: 2019-09-03, 公開日: 2020-09-09, 最終更新日: 2024-11-06)

主引用文献

Shi, X.,Wan, Y.,Wang, N.,Xiang, J.,Wang, T.,Yang, X.,Wang, J.,Dong, X.,Dong, L.,Yan, L.,Li, Y.,Liu, L.,Hou, S.,Zhong, Z.,Wilson, I.A.,Yang, B.,Yang, G.,Lerner, R.A.
Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms.
Nat Commun, 12:2547-2547, 2021

PubMed Abstract: Receptors and their ligands are important therapeutic targets for about one third of marketed drugs. Here, we describe an epitope-guided approach for selection of antibodies that modulate cellular signaling of targeted receptors. We chose CXC chemokine receptor 2 (CXCR2) in the G-protein coupled receptor superfamily as receptor and a CXCR2 N-terminal peptide for antibody selection. We obtain a highly selective, tight-binding antibody from a 10-member antibody library using combinatorial enrichment. Structural and Hydrogen-Deuterium-Exchange mass spectrometry analyses demonstrate antibody interaction with an N-terminal region of CXCR2 that is part of the IL-8 epitope. The antibody strongly inhibits IL-8-induced and CXCR2-mediated neutrophil chemotaxis in vitro and alleviates hCXCR2-dependent experimental autoimmune encephalomyelitis symptoms in mice. As inappropriate neutrophil migration accompanies many diseases including inflammatory bowel disease, glomerulonephritis, allergic asthma, chronic obstructive pulmonary disease, and cancer, this antibody has potential for development as a therapeutic agent, akin to anti-TNF antibodies. However, an important difference here is that the antibody targets the chemokine receptor and competes with natural ligand, rather than targeting the ligand itself.

PubMed: 33953162
DOI: 10.1038/s41467-021-22810-z

実験手法

X-RAY DIFFRACTION (2.2 Å)