4NY0

Crystal structure of FERM domain of human focal adhesion kinase

Summary for 4NY0

• Entry DOI: 10.2210/pdb4ny0/pdb
• Descriptor: Focal adhesion kinase 1 (1 entity in total)
• Functional Keywords: ferm domain, focal adhesion kinase, focal targeting domain, integrin signaling, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell junction, focal adhesion: Q05397
• Total number of polymer chains: 4
• Total formula weight: 172508.31

Authors

Walkiewicz, K.,Arold, S.T. (deposition date: 2013-12-10, release date: 2014-03-12, Last modification date: 2024-03-20)

Primary citation

Brami-Cherrier, K.,Gervasi, N.,Arsenieva, D.,Walkiewicz, K.,Boutterin, M.C.,Ortega, A.,Leonard, P.G.,Seantier, B.,Gasmi, L.,Bouceba, T.,Kadare, G.,Girault, J.A.,Arold, S.T.
FAK dimerization controls its kinase-dependent functions at focal adhesions.
Embo J., 33:356-370, 2014

PubMed Abstract: Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK's kinase-dependent functions--autophosphorylation of tyrosine-397--requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation.

PubMed: 24480479
DOI: 10.1002/embj.201386399

Experimental method

X-RAY DIFFRACTION (2.8 Å)