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1unc
From Proteopedia
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SOLUTION STRUCTURE OF THE HUMAN VILLIN C-TERMINAL HEADPIECE SUBDOMAIN
Contents |
Overview
Headpiece (HP) is a 76-residue F-actin-binding module at the C terminus of many cytoskeletal proteins. Its 35-residue C-terminal subdomain is one of the smallest known motifs capable of autonomously adopting a stable, folded structure in the absence of any disulfide bridges, metal ligands, or unnatural amino acids. We report the three-dimensional solution structures of the C-terminal headpiece subdomains of human villin (HVcHP) and human advillin (HAcHP), determined by two-dimensional 1H-NMR. They represent the second and third structures of such C-terminal headpiece subdomains to be elucidated so far. A comparison with the structure of the chicken villin C-terminal subdomain reveals a high structural conservation. Both C-terminal subdomains bind specifically to F-actin. Mutagenesis is used to demonstrate the involvement of Trp 64 in the F-actin-binding surface. The latter residue is part of a conserved structural feature, in which the surface-exposed indole ring is stacked on the proline and lysine side chain embedded in a PXWK sequence motif. On the basis of the structural and mutational data concerning Trp 64 reported here, the results of a cysteine-scanning mutagenesis study of full headpiece, and a phage display mutational study of the 69-74 fragment, we propose a modification of the model, elaborated by Vardar and coworkers, for the binding of headpiece to F-actin.
Disease
Known diseases associated with this structure: Cholestasis, progressive canalicular OMIM:[193040]
About this Structure
1UNC is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Solution structures of the C-terminal headpiece subdomains of human villin and advillin, evaluation of headpiece F-actin-binding requirements., Vermeulen W, Vanhaesebrouck P, Van Troys M, Verschueren M, Fant F, Goethals M, Ampe C, Martins JC, Borremans FA, Protein Sci. 2004 May;13(5):1276-87. PMID:15096633
Page seeded by OCA on Thu Mar 20 14:34:17 2008
