NMR structure of an F-actin-binding "headpiece" motif from villin

A growing family of F-actin-bundling proteins harbors a modular F-actin-bin ding 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 chic ken villin headpiece (HP67) reveals two subdomains that share a tightly pac ked hydrophobic core. The N-terminal subdomain contains bends, turns, and a four-residue alpha-helix as well as a buried histidine residue that impart s a pH-dependent folding. The C-terminal subdomain is composed of three alp ha-helices and its folding is pH-independent. Two residues previously impli cated in F-actin-binding form a buried salt-bridge between the N and C-term inal subdomains. The rest of the identified actin-binding residues are solv ent-exposed and map onto a unique F-actin-binding surface. (C) 1999 Academi c Press.