Dramatic acceleration of protein folding by stabilization of a nonnative backbone conformation.

ABSTRACT: Through a mutagenic investigation of Gly-48, a highly conserved position in the Src homology 3 domain, we have discovered a series of amino acid substitutions that are highly destabilizing, yet dramatically accelerate protein folding, some up to 10-fold compared with the wild-type rate. The unique folding properties of these mutants allowed for accurate measurement of their folding and unfolding rates in water with no denaturant by using an NMR spin relaxation dispersion technique. A strong correlation was found between beta-sheet propensity and the folding rates of the Gly-48 mutants, even though Gly-48 lies in an unusual non-beta-strand backbone conformation in the native state. This finding indicates that the accelerated folding rates of the Gly-48 mutants are the result of stabilizatio

SUBMITTER: Di Nardo AA 

PROVIDER: S-EPMC419538 | biostudies-literature | 2004 May

REPOSITORIES: biostudies-literature