Molecular and Cellular Biology, July 2005, p. 6112-6122, Vol. 25, No. 14
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.14.6112-6122.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Structural Dynamics of
-Actinin-Vinculin Interactions
Philippe R. J. Bois,1
Robert A. Borgon,2,3
Clemens Vonrhein,4 and
Tina Izard2*
Departments of Biochemistry,1
Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee,2
Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, Tennessee,3
Global Phasing Limited, Sheraton House, Castle Park, Cambridge, United Kingdom4
Received 7 October 2004/
Returned for modification 28 October 2004/
Accepted 11 April 2005
-Actinin and vinculin orchestrate reorganization of the actin cytoskeleton following the formation of adhesion junctions.
-Actinin interacts with vinculin through the binding of an
-helix (
VBS) present within the R4 spectrin repeat of its central rod domain to vinculin's N-terminal seven-helical bundle domain (Vh1). The Vh1:
VBS structure suggests that
VBS first unravels from its buried location in the triple-helical R4 repeat to allow it to bind to vinculin.
VBS binding then induces novel conformational changes in the N-terminal helical bundle of Vh1, which disrupt its intramolecular association with vinculin's tail domain and which differ from the alterations in Vh1 provoked by the binding of talin. Surprisingly,
VBS binds to Vh1 in an inverted orientation compared to the binding of talin's VBSs to vinculin. Importantly, the binding of
VBS and talin's VBSs to vinculin's Vh1 domain appear to also trigger distinct conformational changes in full-length vinculin, opening up distant regions that are buried in the inactive molecule. The data suggest a model where vinculin's Vh1 domain acts as a molecular switch that undergoes distinct structural changes provoked by talin and
-actinin binding in focal adhesions versus adherens junctions, respectively.
* Corresponding author. Mailing address: Department of Hematology-Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105. Phone: (901) 495-3996. Fax: (901) 495-4981. E-mail: tina.izard{at}stjude.org.
Supplemental material for this article may be found at http://mcb.asm.org/.
Molecular and Cellular Biology, July 2005, p. 6112-6122, Vol. 25, No. 14
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.14.6112-6122.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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Copyright © 2005 by the American Society for Microbiology. All rights reserved.