Figure 2.

RyR2 molecule. (A) Three-dimensional structure of RyR2 (Protein Data Bank identification code 6JI0). (B) Regulation of the RyR2 complex. CaM, calmodulin; CaMKII, Ca²⁺/calmodulin-dependent protein kinase II; FKBP, FK506-binding protein; mAKAP, muscle-specific A kinase–anchoring protein; PKA, protein kinase A; PM, plasma membrane; PP1, protein phosphatase 1; PP2A, protein phosphatase 2A; PR130, regulatory subunit of PP2A. (C) Schematic organization of the linear sequence of RyR2 with major structural domains of RyR2 (blue boxes). Orange boxes indicate four disease-associated variant clusters (variant hotspots). Adapted with permission from Zhong et al.⁸⁵