2J0K

Crystal structure of a fragment of focal adhesion kinase containing the FERM and kinase domains.

2J0K の概要

• エントリーDOI: 10.2210/pdb2j0k/pdb
• 関連するPDBエントリー: 1KTM 1PV3 1QVX 2AEH 2AL6 2J0J 2J0L 2J0M
• 分子名称: FOCAL ADHESION KINASE 1, 1,2,3,4-TETRAHYDROGEN-STAUROSPORINE (3 entities in total)
• 機能のキーワード: cell migration, transferase, integrin signaling
• 由来する生物種: GALLUS GALLUS (CHICKEN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 151585.69

構造登録者

Lietha, D.,Cai, X.,Li, Y.,Schaller, M.D.,Eck, M.J. (登録日: 2006-08-03, 公開日: 2007-07-03, 最終更新日: 2023-12-13)

主引用文献

Lietha, D.,Cai, X.,Li, Y.,Schaller, M.D.,Eck, M.J.
Structural Basis for the Autoinhibition of Focal Adhesion Kinase.
Cell(Cambridge,Mass.), 129:1177-, 2007

PubMed Abstract: Appropriate tyrosine kinase signaling depends on coordinated sequential coupling of protein-protein interactions with catalytic activation. Focal adhesion kinase (FAK) integrates signals from integrin and growth factor receptors to regulate cellular responses including cell adhesion, migration, and survival. Here, we describe crystal structures representing both autoinhibited and active states of FAK. The inactive structure reveals a mechanism of inhibition in which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. The active phosphorylated FAK kinase adopts a conformation that is immune to FERM inhibition. Our biochemical and structural analysis shows how the architecture of autoinhibited FAK orchestrates an activation sequence of FERM domain displacement, linker autophosphorylation, Src recruitment, and full catalytic activation.

PubMed: 17574028
DOI: 10.1016/J.CELL.2007.05.041

実験手法

X-RAY DIFFRACTION (3 Å)