Figure 18. Coarse-grained model of CaM, CaMKII, and CaN adapted from Chang et al., 2019 and Pepke et al., 2010.

Figure 18 is adapted from Figure 5 from Pepke et al., 2010. Reaction from the CaM-Ca reactions (first layer) are attributed to 2Ca release and binding from different CaM saturation states CaM2C (2Ca bound to terminal C), CaM2N (2Ca bound to terminal N), CaM0 (no calcium bound), CaM4(Ca bound to both C and N terminal). Note that CaN is allowed to bind only to fully saturated CaM. Activated CaN is represented by the state CaNCaM4. Reactions between the first (CaM-Ca reactions) and the second layer (KCaM-Ca reactions) represent the binding of free/monomeric CaMKII (mKCaM) (Pepke et al., 2010) to different saturation levels of CaM. Reactions within the layer KCaM-Ca represent the binding of calcium to Calmodulin bound to CaMKII (KCaM0, KCaM2C, KCaM2N, KCaM4). Transition of layer KCaM-Ca reactions to layer KCaM-phosphorylation represents CaMKII bound to CaM that became phosphorylated (PCaM states) (Pepke et al., 2010; Chang et al., 2017; Chang et al., 2019). PCaM can become self-phosphorylated (Autonomous layer with P and P2) and release CaM. Once the KCaM deactivates from autonomous states, it returns to free monomeric CaMKII (mKCaM). The CaMKII activity in this work represent the states (KCaM +PCaM + P + P2). See Chang et al., 2019 for further explanation on this system. CaNCaM4 represents the CaN activity. For graphical reasons, we could not show the complete list of reactions as given in Table 12.