Focal adhesions (FAs) are large submembrane signaling complexes formed at sites of cellular attachment to the extracellular matrix. The interaction of LD motifs with their targets plays an important role in the assembly of FAs. We have determined the molecular basis for the recognition of two paxillin LD motifs by the FA targeting (FAT) domain of FA kinase using a combination of X-ray crystallography, solution NMR, and homology modeling. The four-helix FAT domain displays two LD binding sites on opposite sites of the molecule that bind LD peptides in a helical conformation. Threading studies suggest that the LD-interacting domain of p95PKL shares a common four-helical core with the FAT domain and the tail of vinculin, defining a structural family of LD motif binding modules.
Bibliographical noteFunding Information:
We thank P. Carpentier, L. Jacquamet, and J.-L. Ferrer of the ESRF, Grenoble, for their assistance during data recording as well as Jonathan Boyd and Nick Soffe from the NMR facility at Oxford for excellent support. We would also like to thank Robin Aplin and Neil Oldham for mass spectroscopy and Mark Ginsberg for providing us with the initial FAT expression vector. Technical support has been provided by Irene Taylor and Richard Bryan. M.H., J.M.W., and I.D.C. would like to thank the Wellcome Trust for financial support. S.A. and M.E.M.N. would like to thank the MRC for financial support.
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology