8TEC

Crystal structure of Kindlin2 in complex with acylated beta1 integrin peptide

8TEC の概要

• エントリーDOI: 10.2210/pdb8tec/pdb
• 関連するPDBエントリー: 5xpy
• 分子名称: Fermitin family homolog 2, Integrin beta-1 (3 entities in total)
• 機能のキーワード: kindlin, integrin, acylation, cell adhesion
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 124217.32

構造登録者

Zhang, P.F.,Wu, J.H. (登録日: 2023-07-06, 公開日: 2024-07-03, 最終更新日: 2024-10-30)

主引用文献

Sidibe, A.,Mykuliak, V.V.,Zhang, P.,Hytonen, V.P.,Wu, J.,Wehrle-Haller, B.
Acetyl-NPKY of integrin-beta 1 binds KINDLIN2 to control endothelial cell proliferation and junctional integrity.
Iscience, 27:110129-110129, 2024

PubMed Abstract: Integrin-dependent crosstalk between cell-matrix adhesions and cell-cell junctions is critical for controlling endothelial permeability and proliferation in cancer and inflammatory diseases but remains poorly understood. Here, we investigated how acetylation of the distal NPKY-motif of Integrin-β1 influences endothelial cell physiology and barrier function. Expression of an acetylation-mimetic β1-K794Q-GFP mutant led to the accumulation of immature cell-matrix adhesions accompanied by a transcriptomic reprograming of endothelial cells, involving genes associated with cell adhesion, proliferation, polarity, and barrier function. β1-K794Q-GFP induced constitutive MAPK signaling, junctional impairment, proliferation, and reduced contact inhibition at confluence. Structural analysis of Integrin-β1 interaction with KINDLIN2, biochemical pulldown assay, and binding energy determination by using molecular dynamics simulation showed that acetylation of K794 and the K794Q-mutant increased KINDLIN2 binding affinity to the Integrin-β1. Thus, enhanced recruitment of KINDLIN2 to Lysine-acetylated Integrin-β1 and resulting modulation of barrier function, offers new therapeutic possibilities for controlling vascular permeability and disease conditions.

PubMed: 38904068
DOI: 10.1016/j.isci.2024.110129

実験手法

X-RAY DIFFRACTION (2.04 Å)