2j0m
CRYSTAL STRUCTURE A TWO-CHAIN COMPLEX BETWEEN THE FERM AND KINASE DOMAINS OF FOCAL ADHESION KINASE.
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OverviewOverview
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.
About this StructureAbout this Structure
2J0M is a Single protein structure of sequence from Gallus gallus with as ligand. Active as Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for the autoinhibition of focal adhesion kinase., Lietha D, Cai X, Ceccarelli DF, Li Y, Schaller MD, Eck MJ, Cell. 2007 Jun 15;129(6):1177-87. PMID:17574028
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