1unc

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SOLUTION STRUCTURE OF THE HUMAN VILLIN C-TERMINAL HEADPIECE SUBDOMAIN

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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] with ACE as ligand. 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

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