Subdomain competition, cooperativity, and topological frustration in the folding of CheY.

ABSTRACT: The folding of multidomain proteins often proceeds in a hierarchical fashion with individual domains folding independent of one another. A large single-domain protein, however, can consist of multiple modules whose folding may be autonomous or interdependent in ways that are unclear. We used coarse-grained simulations to explore the folding landscape of the two-subdomain bacterial response regulator CheY. Thermodynamic and kinetic characterization shows the landscape to be highly analogous to the four-state landscape reported for another two-subdomain protein, T4 lysozyme. An on-pathway intermediate structured in the more stable nucleating subdomain was observed, as were transient states frustrated in off-pathway contacts prematurely structured in the weaker subdomain. Local unfolding, or

SUBMITTER: Hills RD 

PROVIDER: S-EPMC2564871 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature