Unidirectional allostery in the regulatory subunit RIα facilitates efficient deactivation of protein kinase A.

ABSTRACT: The holoenzyme complex of protein kinase A is in an inactive state; activation involves ordered cAMP binding to two tandem domains of the regulatory subunit and release of the catalytic subunit. Deactivation has been less studied, during which the two cAMPs unbind from the regulatory subunit to allow association of the catalytic subunit to reform the holoenzyme complex. Unbinding of the cAMPs appears ordered as indicated by a large difference in unbinding rates from the two sites, but the cause has remained elusive given the structural similarity of the two tandem domains. Even more intriguingly, NMR data show that allosteric communication between the two domains is unidirectional. Here, we present a mechanism for the unidirectionality, developed from extensive molecular dynamics simulatio

SUBMITTER: Guo C 

PROVIDER: S-EPMC5098638 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature