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STRUCTURE/FUNCTION OF VINCULIN IN FOCAL ADHESIONS

$375,100R01FY2002GMNIH

Burnham Institute For Medical Research, La Jolla CA

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Abstract

DESCRIPTION: A structural analysis of the focal contact protein vinculin is proposed. Using a combination of X-ray crystallography and NMR, it is proposed to determine atomic models of full-length vinculin as well as isolated domains, and then determine the structures of complexes with binding-protein fragments. These data will be used to map out binding sites which, by reference to the structure of the intact molecule, will also suggest how binding is regulated. Using this information, mutants lacking specific functions will be generated and their ability to rescue vinculin null cells assessed in vivo.

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