Integrating folding kinetics and protein function: biphasic kinetics and dual binding specificity in a WW domain.

ABSTRACT: Because of the association of beta-sheet formation with the initiation and propagation of amyloid diseases, model systems have been sought to further our understanding of this process. WW domains have been proposed as one such model system. Whereas the folding of the WW domains from human Yes-associated protein (YAP) and Pin have been shown to obey single-exponential kinetics, the folding of the WW domain from formin-binding protein (FBP) 28 has been shown to proceed via biphasic kinetics. From an analysis of free-energy landscapes from atomic-level molecular dynamics simulations, the biphasic folding kinetics observed in the FBP WW domain may be traced to the ability of this WW domain to adopt two slightly different forms of packing in its hydrophobic core. This conformational change is p

SUBMITTER: Karanicolas J 

PROVIDER: S-EPMC373479 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature