Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins.

ABSTRACT: Elucidating the complex interplay between protein structure and dynamics is a prerequisite to an understanding of both function and adaptation in proteins. Unfortunately, it has been difficult to experimentally decouple these effects because it is challenging to rationally design mutations that will either affect the structure but not the dynamics, or that will affect the dynamics but not the structure. Here we adopt a mutation approach that is based on a thermal adaptation strategy observed in nature, and we use it to study the binding interaction of Escherichia coli adenylate kinase (AK). We rationally design several single-site, surface-exposed glycine mutations to selectively perturb the excited state conformational repertoire, leaving the ground-state X-ray crystallographic structure

SUBMITTER: Schrank TP 

PROVIDER: S-EPMC2761315 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature