2KNC

Platelet integrin ALFAIIB-BETA3 transmembrane-cytoplasmic heterocomplex

2KNC の概要

• エントリーDOI: 10.2210/pdb2knc/pdb
• NMR情報: BMRB: 16496
• 分子名称: Integrin alpha-IIb, Integrin beta-3 (2 entities in total)
• 機能のキーワード: integrin, transmembrane signaling, protein structure, cell adhesion, cleavage on pair of basic residues, disease mutation, disulfide bond, glycoprotein, membrane, pyrrolidone carboxylic acid, receptor, transmembrane, host-virus interaction, phosphoprotein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14832.34

構造登録者

Yang, J.,Ma, Y.,Page, R.C.,Misra, S.,Plow, E.F.,Qin, J. (登録日: 2009-08-20, 公開日: 2009-09-29, 最終更新日: 2024-05-08)

主引用文献

Yang, J.,Ma, Y.Q.,Page, R.C.,Misra, S.,Plow, E.F.,Qin, J.
Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation.
Proc.Natl.Acad.Sci.USA, 106:17729-17734, 2009

PubMed Abstract: Heterodimeric integrin adhesion receptors regulate diverse biological processes including angiogenesis, thrombosis and wound healing. The transmembrane-cytoplasmic domains (TMCDs) of integrins play a critical role in controlling activation of these receptors via an inside-out signaling mechanism, but the precise structural basis remains elusive. Here, we present the solution structure of integrin alphaIIb beta3 TMCD heterodimer, which reveals a right-handed coiled-coil conformation with 2 helices intertwined throughout the transmembrane region. The helices extend into the cytoplasm and form a clasp that differs significantly from a recently published alphaIIb beta3 TMCD structure. We show that while a point mutation in the clasp interface modestly activates alphaIIb beta3, additional mutations in the transmembrane interface have a synergistic effect, leading to extensive integrin activation. Detailed analyses and structural comparison with previous studies suggest that extensive integrin activation is a highly concerted conformational transition process, which involves transmembrane coiled-coil unwinding that is triggered by the membrane-mediated alteration and disengagement of the membrane-proximal clasp. Our results provide atomic insight into a type I transmembrane receptor heterocomplex and the mechanism of integrin inside-out transmembrane signaling.

PubMed: 19805198
DOI: 10.1073/pnas.0909589106

実験手法

SOLUTION NMR