3V4P

crystal structure of a4b7 headpiece complexed with Fab ACT-1

3V4P の概要

• エントリーDOI: 10.2210/pdb3v4p/pdb
• 関連するPDBエントリー: 3V4V
• 分子名称: Integrin alpha-4, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, Integrin beta-7, ... (11 entities in total)
• 機能のキーワード: cell adhesion, madcam-1, membrane
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 342666.70

構造登録者

Yu, Y.,Zhu, J.,Springer, T.A. (登録日: 2011-12-15, 公開日: 2012-01-11, 最終更新日: 2024-10-09)

主引用文献

Yu, Y.,Zhu, J.,Mi, L.Z.,Walz, T.,Sun, H.,Chen, J.,Springer, T.A.
Structural specializations of a4b7, an Integrin that Mediates Rolling Adhesion
J.Cell Biol., 196:131-146, 2012

PubMed Abstract: The lymphocyte homing receptor integrin α(4)β(7) is unusual for its ability to mediate both rolling and firm adhesion. α(4)β(1) and α(4)β(7) are targeted by therapeutics approved for multiple sclerosis and Crohn's disease. Here, we show by electron microscopy and crystallography how two therapeutic Fabs, a small molecule (RO0505376), and mucosal adhesion molecule-1 (MAdCAM-1) bind α(4)β(7). A long binding groove at the α(4)-β(7) interface for immunoglobulin superfamily domains differs in shape from integrin pockets that bind Arg-Gly-Asp motifs. RO0505376 mimics an Ile/Leu-Asp motif in α(4) ligands, and orients differently from Arg-Gly-Asp mimics. A novel auxiliary residue at the metal ion-dependent adhesion site in α(4)β(7) is essential for binding to MAdCAM-1 in Mg(2+) yet swings away when RO0505376 binds. A novel intermediate conformation of the α(4)β(7) headpiece binds MAdCAM-1 and supports rolling adhesion. Lack of induction of the open headpiece conformation by ligand binding enables rolling adhesion to persist until integrin activation is signaled.

PubMed: 22232704
DOI: 10.1083/jcb.201110023

実験手法

X-RAY DIFFRACTION (3.15 Å)