Structural elements within RyR2 important for channel activation. The dotted line divides structures from the neighboring subunits. The EF-hand domain of one subunit may interact with the VSL_cyt of the neighboring unit. The Ca²⁺-binding site, caffeine-binding site, ATP-binding site, E4872 Ca²⁺-binding pocket, and contact site between the EF-hand domain and the VSL_cyt domain are highlighted by red dashed ellipses. Locations are based on des Georges et al. (2016).