1UND

Solution structure of the human advillin C-terminal headpiece subdomain

Summary for 1UND

• Entry DOI: 10.2210/pdb1und/pdb
• NMR Information: BMRB: 5966
• Descriptor: ADVILLIN (1 entity in total)
• Functional Keywords: actin binding, f-actin binding, cytoskeleton, headpiece subdomain
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, cytoskeleton: O75366
• Total number of polymer chains: 1
• Total formula weight: 4179.86

Authors

Vermeulen, W.,Van Troys, M.,Vanhaesebrouck, P.,Verschueren, M.,Fant, F.,Ampe, C.,Martins, J.,Borremans, F. (deposition date: 2003-09-09, release date: 2004-07-15, Last modification date: 2024-10-16)

Primary citation

Vermeulen, W.,Vanhaesebrouck, P.,Van Troys, M.,Verschueren, M.,Fant, F.,Goethals, M.,Ampe, C.,Martins, J.,Borremans, F.
Solution Structures of the C-Terminal Headpiece Subdomains of Human Villin and Advillin, Evaluation of Headpiece F-Actin-Binding Requirements
Protein Sci., 13:1276-, 2004

PubMed Abstract: 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.

PubMed: 15096633
DOI: 10.1110/PS.03518104

Experimental method

SOLUTION NMR