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CRYSTAL STRUCTURE OF A THE ACTIVE CONFORMATION OF THE KINASE DOMAIN OF FOCAL ADHESION KINASE WITH A PHOSPHORYLATED ACTIVATION LOOP.CRYSTAL STRUCTURE OF A THE ACTIVE CONFORMATION OF THE KINASE DOMAIN OF FOCAL ADHESION KINASE WITH A PHOSPHORYLATED ACTIVATION LOOP.
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAppropriate 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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