Non-native interactions are critical for mechanical strength in PKD domains.

ABSTRACT: Experimental observation has led to the commonly held view that native state protein topology is the principle determinant of mechanical strength. However, the PKD domains of polycystin-1 challenge this assumption: they are stronger than predicted from their native structure. Molecular dynamics simulations suggest that force induces rearrangement to an intermediate structure, with nonnative hydrogen bonds, that resists unfolding. Here we test this hypothesis directly by introducing mutations designed to prevent formation of these nonnative interactions. We find that these mutations, which only moderately destabilize the native state, reduce the mechanical stability dramatically. The results demonstrate that nonnative interactions impart significant mechanical stability, necessary for the m

SUBMITTER: Forman JR 

PROVIDER: S-EPMC2862302 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature