Activation State-Dependent Substrate Gating in Ca²⁺/Calmodulin-Dependent Protein Kinase II

Figure 1

Molecular structure and schematic models for CaMKII autoregulation and activation. (a–c) Structural representations of CaMKII’s catalytic domain (green), autoregulatory domain (ARD) (blue), and hub domain (gray). (a) Illustration of CaMKII holoenzyme with detailed view of the catalytic domain. Adapted X-ray crystal structure shows monomeric human CaMKIIδ_11–309 (PDB ID: 2VN9; [11]) in the autoinhibited state with the ARD (blue) and modified to include ATP in the active site (PDB ID: 1ATP; [71]). (b) hCaMKIIδ_11–335 activated (PDB ID: 2WEL; [11]) by Ca²⁺ (red spheres) and calmodulin (CaM) (magenta) and exposing T²⁸⁷ (white) for autophosphorylation. (c) Linear schematic of CaMKII holoenzyme (CaMKII_holo) and monomeric CaMKII (CaMKII_m, or CaMKII_1–317). Expanded view shows the ARD (blue) with subdivisions R1 (T²⁸⁷ containing region) and R2/R3 (CaM-binding region) [72].