The catenins (a-catenin, b-catenin and plakoglobin) are cytoplasmic proteins that link cadherin cell adhesion molecules to the cytoskeleton. Catenins are required for functional cell adhesion, and are the targets of regulatory signals that control cell adhesion. B-Catenin, plakoglobin, and their Drosophila homolog, Armadillo, are also critical components of the wnt-1/wingless signaling pathway that controls cell fate determination during development. The goal of this proposal is to understand the interactions among the catenins and their binding partners both biochemically and structurally. 1. The three-dimensional structures of b-catenin, plakoglobin, and their complexes with classical cadherin cytoplasmic domains and a-catenin, will be determined by x-ray crystallography. 2. The binding stoichiometries and affinities for the interaction of b-catenin with the E-cadherin cytoplasmic domain and with a-catenin will be measured by standard biochemical methods and surface plasmon resonance detection. 3. The affinities and structures of plakoglobin interactions with E-cadherin, desmosomal cadherins and with a-catenin will be determined in order to understand the unique properties of plakoglobin that allow it to be localized both in adherens junctions and desmosomes.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Physiological Chemistry Study Section (PC)
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Lewis, Catherine D
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Stanford University
Schools of Medicine
United States
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Kang, Hyunook; Weiss, Thomas M; Bang, Injin et al. (2016) Structure of the Intermediate Filament-Binding Region of Desmoplakin. PLoS One 11:e0147641
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