Role of dynamics in the autoinhibition and activation of the exchange protein directly activated by cyclic AMP (EPAC).

ABSTRACT: The exchange protein directly activated by cAMP (EPAC) is a key receptor of cAMP in eukaryotes and controls critical signaling pathways. Currently, no residue resolution information is available on the full-length EPAC dynamics, which are known to be pivotal determinants of allostery. In addition, no information is presently available on the intermediates for the classical induced fit and conformational selection activation pathways. Here these questions are addressed through molecular dynamics simulations on five key states along the thermodynamic cycle for the cAMP-dependent activation of a fully functional construct of EPAC2, which includes the cAMP-binding domain and the integral catalytic region. The simulations are not only validated by the agreement with the experimental trends in c

SUBMITTER: VanSchouwen B 

PROVIDER: S-EPMC3234915 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature