2L1C

Shc-PTB:biphosphorylated integrin beta3 cytoplasmic tail complex (1:1)

2L1C の概要

• エントリーDOI: 10.2210/pdb2l1c/pdb
• NMR情報: BMRB: 17080
• 分子名称: SHC (Src homology 2 domain containing) transforming protein 1, isoform CRA_d, Integrin beta-3 (2 entities in total)
• 機能のキーワード: shc-ptb, integrin beta3, cytoplasmic tail, cell adhesion
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05106
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26451.86

構造登録者

Deshmukh, L.,Gorbatyuk, V.,Vinogradova, O. (登録日: 2010-07-27, 公開日: 2010-08-18, 最終更新日: 2024-10-09)

主引用文献

Deshmukh, L.,Gorbatyuk, V.,Vinogradova, O.
Integrin {beta}3 phosphorylation dictates its complex with the Shc phosphotyrosine-binding (PTB) domain.
J.Biol.Chem., 285:34875-34884, 2010

PubMed Abstract: Adaptor protein Shc plays a key role in mitogen-activated protein kinase (MAPK) signaling pathway, which can be mediated through a number of different receptors including integrins. By specifically recognizing the tyrosine-phosphorylated integrin β(3), Shc has been shown to trigger integrin outside-in signaling, although the structural basis of this interaction remains nebulous. Here we present the detailed structural analysis of Shc phosphotyrosine-binding (PTB) domain in complex with the bi-phosphorylated β(3)integrin cytoplasmic tail (CT). We show that this complex is primarily defined by the phosphorylation state of the integrin C-terminal Tyr(759), which fits neatly into the classical PTB pocket of Shc. In addition, we have identified a novel binding interface which concurrently accommodates phosphorylated Tyr(747) of the highly conserved NPXY motif of β(3). The structure represents the first snapshot of an integrin cytoplasmic tail bound to a target for mediating the outside-in signaling. Detailed comparison with the known Shc PTB structure bound to a target TrkA peptide revealed some significant differences, which shed new light upon the PTB domain specificity.

PubMed: 20739287
DOI: 10.1074/jbc.M110.159087

実験手法

SOLUTION NMR