Figure 5. A simplified schematic diagram showing the key pathways for autophosphorylation at the activating and inhibitory sites, in the absence or presence of Ca²⁺/CaM.

While Thr 305/306 can get phosphorylated both in cis in the absence of Ca²⁺/CaM or in trans in the presence of Ca²⁺/CaM, autophosphorylation of Thr 286 can only happen in trans in the presence of Ca²⁺/CaM. Ca²⁺/CaM shows a rapid association and dissociation until CaMKII gets phosphorylated at Thr 286, when its affinity for Ca²⁺/CaM increases by about 1000-fold. A detailed description of all the different reactions and conditions that form the basis of our kinetic model is provided in the Appendix.

Figure 5—figure supplement 1. Results from simulations of a simple kinetic model for autophosphorylation in CaMKII using Berkeley Madonna.

Plot showing the production of all species bearing pThr 286 or pThr 305/306 over simulation time, when (a) the linker-length is short with faster rates of trans-autophosphorylation and when (b) the linker-length is long and the rates of trans-autophosphorylation are 10-fold slower.