K.W. Walkiewicz, J.A. Girault, S.T. Arold
Prog Biophys Mol Biol.,
119(1), pp. 60-71, (2015)
Multidomain protein; Adhesome; X-ray crystallography; Molecular dynamics; Hybrid methods; Calcium signalling
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.