Molecular recognition of paxillin LD motifs by the focal adhesion targeting domain

Maria K. Hoellerer; Martin E.M. Noble; Gilles Labesse; Iain D. Campbell; Jörn M. Werner; Stefan T. Arold

doi:10.1016/j.str.2003.08.010

Molecular recognition of paxillin LD motifs by the focal adhesion targeting domain

Maria K. Hoellerer, Martin E.M. Noble, Gilles Labesse, Iain D. Campbell, Jörn M. Werner^*, Stefan T. Arold

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

87 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1207-1217
Number of pages	11
Journal	Structure
Volume	11
Issue number	10
DOIs	https://doi.org/10.1016/j.str.2003.08.010
State	Published - Oct 1 2003
Externally published	Yes

Bibliographical note

Funding 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

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title = "Molecular recognition of paxillin LD motifs by the focal adhesion targeting domain",

abstract = "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.",

author = "Hoellerer, {Maria K.} and Noble, {Martin E.M.} and Gilles Labesse and Campbell, {Iain D.} and Werner, {J{\"o}rn M.} and Arold, {Stefan T.}",

note = "Funding 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. ",

year = "2003",

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doi = "10.1016/j.str.2003.08.010",

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AU - Hoellerer, Maria K.

AU - Noble, Martin E.M.

AU - Labesse, Gilles

AU - Campbell, Iain D.

AU - Werner, Jörn M.

AU - Arold, Stefan T.

N1 - Funding 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.

PY - 2003/10/1

Y1 - 2003/10/1

N2 - 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.

AB - 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.

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Molecular recognition of paxillin LD motifs by the focal adhesion targeting domain

Abstract

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