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The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix bundle that binds paxillin

Nature Structural Biology volume 9, pages 101–106 (2002)Cite this article

Abstract

Focal adhesion kinase (FAK) is a tyrosine kinase found in focal adhesions, intracellular signaling complexes that are formed following engagement of the extracellular matrix by integrins. The C-terminal 'focal adhesion targeting' (FAT) region is necessary and sufficient for localizing FAK to focal adhesions. We have determined the crystal structure of FAT and show that it forms a four-helix bundle that resembles those found in two other proteins involved in cell adhesion, α-catenin and vinculin. The binding of FAT to the focal adhesion protein, paxillin, requires the integrity of the helical bundle, whereas binding to another focal adhesion protein, talin, does not. We show by mutagenesis that paxillin binding involves two hydrophobic patches on opposite faces of the bundle and propose a model in which two LD motifs of paxillin adopt amphipathic helices that augment the hydrophobic core of FAT, creating a six-helix bundle.

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Figure 1: Domain structure of FAK and sequence alignments of the FAT domain.
Figure 2: Crystal structure of FAT.
Figure 3: Structural comparisons and surface properties of FAT.
Figure 4: A model of the FAT–paxillin interaction a, Hypothetical model (stereo) of the LD2 peptide (purple) docked onto FAT (gray).

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Acknowledgements

We are grateful to the Brookhaven National Laboratory for synchrotron access. Supported by grants from the NIH to R.C.L. and K.V.

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  1. Program on Cell Adhesion, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, California, USA

    Ikuko Hayashi, Kristiina Vuori & Robert C. Liddington

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  1. Ikuko Hayashi
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  2. Kristiina Vuori
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  3. Robert C. Liddington
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Correspondence to Robert C. Liddington.

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Hayashi, I., Vuori, K. & Liddington, R. The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix bundle that binds paxillin. Nat Struct Mol Biol 9, 101–106 (2002). https://doi.org/10.1038/nsb755

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