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R01 GM071596A1 - PROGRAM NARRATIVE Cells require distinct adhesion complexes at their cell surface to form contacts with their neighbors or with the extracellular environment, and the protein vinculin plays essential roles in linking these adhesion complexes to the actin cytoskeleton, and in directing the cell migration machinery. The formation of these links requires that vinculin transition from its closed, inactive conformation to its activated state, and the studies supported by R01 GM071596 defined the structure of inactive and activated vinculin, and revealed its mechanism of activation. However, essentially nothing is known regarding the interactions of activated vinculin with its binding partners in the cell, and our new studies in this revised competitive renewal application of R01 GM071596 will define the structure and function of vinculin in complex with three of its partners that play essential roles in adhesion complexes, in cell migration, and in the localized production of components of adhesion junctions.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Macromolecular Structure and Function C Study Section (MSFC)
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Flicker, Paula F
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Scripps Florida
United States
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Rangarajan, Erumbi S; Izard, Tina (2013) Dimer asymmetry defines ?-catenin interactions. Nat Struct Mol Biol 20:188-93
Lee, Jun Hyuck; Rangarajan, Erumbi S; Vonrhein, Clemens et al. (2012) The metavinculin tail domain directs constitutive interactions with raver1 and vinculin RNA. J Mol Biol 422:697-704
Rangarajan, Erumbi S; Lee, Jun Hyuck; Izard, Tina (2011) Apo raver1 structure reveals distinct RRM domain orientations. Protein Sci :
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Nhieu, Guy Tran Van; Izard, Tina (2007) Vinculin binding in its closed conformation by a helix addition mechanism. EMBO J 26:4588-96
St-Jean, Miguel; Izard, Tina; Sygusch, Jurgen (2007) A hydrophobic pocket in the active site of glycolytic aldolase mediates interactions with Wiskott-Aldrich syndrome protein. J Biol Chem 282:14309-15

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