7C3M

Structure of FERM protein

7C3M の概要

• エントリーDOI: 10.2210/pdb7c3m/pdb
• 分子名称: Fermitin family homolog 3,Fermitin family homolog 3,Fermitin family homolog 3 (1 entity in total)
• 機能のキーワード: ferm protein, kindlin, integrin, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 229388.25

構造登録者

Bu, W.,Loh, Z.Y.,Jin, S.,Basu, S.,Ero, R.,Park, J.E.,Yan, X.,Wang, M.,Sze, S.K.,Tan, S.M.,Gao, Y.G. (登録日: 2020-05-13, 公開日: 2020-06-03, 最終更新日: 2024-03-27)

主引用文献

Bu, W.,Levitskaya, Z.,Loh, Z.Y.,Jin, S.,Basu, S.,Ero, R.,Yan, X.,Wang, M.,Ngan, S.F.C.,Sze, S.K.,Tan, S.M.,Gao, Y.G.
Structural basis of human full-length kindlin-3 homotrimer in an auto-inhibited state.
Plos Biol., 18:e3000755-e3000755, 2020

PubMed Abstract: Kindlin-1, -2, and -3 directly bind integrin β cytoplasmic tails to regulate integrin activation and signaling. Despite their functional significance and links to several diseases, structural information on full-length kindlin proteins remains unknown. Here, we report the crystal structure of human full-length kindlin-3, which reveals a novel homotrimer state. Unlike kindlin-3 monomer, which is the major population in insect and mammalian cell expression systems, kindlin-3 trimer does not bind integrin β cytoplasmic tail as the integrin-binding pocket in the F3 subdomain of 1 protomer is occluded by the pleckstrin homology (PH) domain of another protomer, suggesting that kindlin-3 is auto-inhibited upon trimer formation. This is also supported by functional assays in which kindlin-3 knockout K562 erythroleukemia cells reconstituted with the mutant kindlin-3 containing trimer-disrupting mutations exhibited an increase in integrin-mediated adhesion and spreading on fibronectin compared with those reconstituted with wild-type kindlin-3. Taken together, our findings reveal a novel mechanism of kindlin auto-inhibition that involves its homotrimer formation.

PubMed: 32644996
DOI: 10.1371/journal.pbio.3000755

実験手法

X-RAY DIFFRACTION (3.6 Å)