Competition between intradomain and interdomain interactions: a buried salt bridge is essential for villin headpiece folding and actin binding.

ABSTRACT: Villin-type headpiece domains are ∼70 residue motifs that reside at the C-terminus of a variety of actin-associated proteins. Villin headpiece (HP67) is a commonly used model system for both experimental and computational studies of protein folding. HP67 is made up of two subdomains that form a tightly packed interface. The isolated C-terminal subdomain of HP67 (HP35) is one of the smallest autonomously folding proteins known. The N-terminal subdomain requires the presence of the C-terminal subdomain to fold. In the structure of HP67, a conserved salt bridge connects N- and C-terminal subdomains. This buried salt bridge between residues E39 and K70 is unusual in a small protein domain. We used mutational analysis, monitored by CD and NMR, and functional assays to determine the role of this

SUBMITTER: Packer LE 

PROVIDER: S-EPMC3086997 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature