A single destabilizing mutation (F9S) promotes concerted unfolding of an entire globular domain in gammaS-crystallin.

ABSTRACT: Conformational change and aggregation of native proteins are associated with many serious age-related and neurological diseases. gammaS-Crystallin is a highly stable, abundant structural component of vertebrate eye lens. A single F9S mutation in the N-terminal domain of mouse gammaS-crystallin causes the severe Opj cataract, with disruption of cellular organization and appearance of fibrillar structures in the lens. Although the mutant protein has a near-native fold at room temperature, significant increases in hydrogen/deuterium exchange rates were observed by NMR for all the well-protected beta-sheet core residues throughout the entire N-terminal domain of the mutant protein, resulting in up to a 3.5-kcal/mol reduction in the free energy of the folding/unfolding equilibrium. No differenc

SUBMITTER: Lee S 

PROVIDER: S-EPMC2904975 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature