2MTP

The structure of Filamin repeat 21 bound to integrin

2MTP の概要

• エントリーDOI: 10.2210/pdb2mtp/pdb
• NMR情報: BMRB: 25176
• 分子名称: Filamin-A, Integrin alpha-IIb, Integrin beta-3 (3 entities in total)
• 機能のキーワード: integrin, filamin, protein binding-cell adhesion complex, protein binding/cell adhesion
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cell cortex: P21333; Membrane; Single-pass type I membrane protein: P08514; Cell membrane ; Single- pass type I membrane protein : P05106
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 17962.83

構造登録者

Liu, J.,Qin, J. (登録日: 2014-08-28, 公開日: 2015-04-01, 最終更新日: 2024-05-15)

主引用文献

Liu, J.,Das, M.,Yang, J.,Ithychanda, S.S.,Yakubenko, V.P.,Plow, E.F.,Qin, J.
Structural mechanism of integrin inactivation by filamin.
Nat.Struct.Mol.Biol., 22:383-389, 2015

PubMed Abstract: Activation of heterodimeric (αβ) integrin is crucial for regulating cell adhesion. Binding of talin to the cytoplasmic face of integrin activates the receptor, but how integrin is maintained in a resting state to counterbalance its activation has remained obscure. Here, we report the structure of the cytoplasmic domain of human integrin αIIbβ3 bound to its inhibitor, the immunoglobin repeat 21 of filamin A (FLNa-Ig21). The structure reveals an unexpected ternary complex in which FLNa-Ig21 not only binds to the C terminus of the integrin β3 cytoplasmic tail (CT), as previously predicted, but also engages N-terminal helices of αIIb and β3 CTs to stabilize an inter-CT clasp that helps restrain the integrin in a resting state. Combined with functional data, the structure reveals a new mechanism of filamin-mediated retention of inactive integrin, suggesting a new framework for understanding regulation of integrin activation and adhesion.

PubMed: 25849143
DOI: 10.1038/nsmb.2999

実験手法

SOLUTION NMR