CaMKII activation and dynamics are independent of the holoenzyme structure: an infinite subunit holoenzyme approximation.

ABSTRACT: The combinatorial explosion produced by the multi-state, multi-subunit character of CaMKII has made analysis and modeling of this key signaling protein a significant challenge. Using rule-based and particle-based approaches, we construct exact models of CaMKII holoenzyme dynamics and study these models as a function of the number of subunits per holoenzyme, N. Without phosphatases the dynamics of activation are independent of the holoenzyme structure unless phosphorylation significantly alters the kinase activity of a subunit. With phosphatases the model is independent of holoenzyme size for N > 6. We introduce an infinite subunit holoenzyme approximation (ISHA), which simplifies the modeling by eliminating the combinatorial complexities encountered in any finite holoenzyme model. The ISHA

SUBMITTER: Michalski PJ 

PROVIDER: S-EPMC3507550 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature