title: How to awaken your nanomachines: Site-specific activation of focal adhesion kinases through ligand interactions.
abstract: The focal adhesion kinase (FAK) and the related protein-tyrosine kinase 2-beta (Pyk2) are highly versatile multidomain scaffolds central to cell adhesion, migration, and survival. Due to their key role in cancer metastasis, understanding and inhibiting their functions are important for the development of targeted therapy. Because FAK and Pyk2 are involved in many different cellular functions, designing drugs with partial and function-specific inhibitory effects would be desirable. Here, we summarise recent progress in understanding the structural mechanism of how the tug-of-war between intramolecular and intermolecular interactions allows these protein 'nanomachines' to become activated in a site-specific manner.
authors.affiliation: King Abdullah University of Science and Technology (KAUST), Division of Biological and Environmental Sciences and Engineering, Computational Bioscience Research Center (CBRC), Thuwal, Saudi Arabia.
authors.forename: Katarzyna W
authors.initials: KW
authors.lastname: Walkiewicz
authors.affiliation: Inserm, UMR-S 839, F-75005 Paris, France; Université Pierre & Marie Curie (UPMC), Sorbonne Universités, F-75005 Paris, France; Institut du Fer à Moulin, F-75005 Paris, France.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
authors.affiliation: King Abdullah University of Science and Technology (KAUST), Division of Biological and Environmental Sciences and Engineering, Computational Bioscience Research Center (CBRC), Thuwal, Saudi Arabia. Electronic address: stefan.arold@kaust.edu.sa.
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Arold
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055808:Drug Discovery; D004789:Enzyme Activation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D008024:Ligands; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: Adhesome; Calcium signalling; Hybrid methods; Molecular dynamics; Multidomain protein; X-ray crystallography