title: NMR structure of an F-actin-binding "headpiece" motif from villin.
abstract: A growing family of F-actin-bundling proteins harbors a modular F-actin-binding headpiece domain at the C terminus. Headpiece provides one of the two F-actin-binding sites essential for filament bundling. Here, we report the first structure of a functional headpiece domain. The NMR structure of chicken villin headpiece (HP67) reveals two subdomains that share a tightly packed hydrophobic core. The N-terminal subdomain contains bends, turns, and a four-residue alpha-helix as well as a buried histidine residue that imparts a pH-dependent folding. The C-terminal subdomain is composed of three alpha-helices and its folding is pH-independent. Two residues previously implicated in F-actin-binding form a buried salt-bridge between the N and C-terminal subdomains. The rest of the identified actin-binding residues are solvent-exposed and map onto a unique F-actin-binding surface.
authors.affiliation: Department of Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA.
authors.forename: D
authors.initials: D
authors.lastname: Vardar
authors.forename: D A
authors.initials: DA
authors.lastname: Buckley
authors.forename: B S
authors.initials: BS
authors.lastname: Frank
authors.forename: C J
authors.initials: CJ
authors.lastname: McKnight
mesh_terms: D000199:Actins / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002645:Chickens; D016384:Consensus Sequence; D006639:Histidine / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents; D055672:Static Electricity; D013816:Thermodynamics; D017186:Titrimetry
chemical_list: D000199:Actins; D002352:Carrier Proteins; D008840:Microfilament Proteins; D010446:Peptide Fragments; D012997:Solvents; C026615:villin; D006639:Histidine