Molecular crowding enhances native state stability and refolding rates of globular proteins.

ABSTRACT: The presence of macromolecules in cells geometrically restricts the available space for poplypeptide chains. To study the effects of macromolecular crowding on folding thermodynamics and kinetics, we used an off-lattice model of the all-beta-sheet WW domain in the presence of large spherical particles whose interaction with the polypeptide chain is purely repulsive. At all volume fractions, phi(c), of the crowding agents the stability of the native state is enhanced. Remarkably, the refolding rates, which are larger than the value at phi(c) = 0, increase nonmonotonically as phi(c) increases, reaching a maximum at phi(c)=phi(c)(*). At high values of phi(c), the depletion-induced intramolecular attraction produces compact structures with considerable structure in the denatured state. Changes

SUBMITTER: Cheung MS 

PROVIDER: S-EPMC555696 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature