Control of cardiac ryanodine receptor by sarcoplasmic reticulum luminal Ca2+

Figure 1.. Three-dimensional structure of RyR2. Three-dimensional structure of RyR2 showing two opposing subunits (Peng et al., 2016). Boxes highlight the structures shown in more detail in Figs. 2 A and 3.

Figure 2.. Structure of the RyR2 channel pore. (A) Detailed structure of the channel pore of RyR2, illustrating the major structural elements potentially involved in Ca2+ activation. (B) Top view of the channel pore, showing salt bridges potentially formed between D4868, E4872, and R4874. (C) Top view of the channel pore in a closed (left) and open (right) conformation. In the closed state, the constriction point (the narrowest part of the pore) is formed by I4867; when the channel opens, the constriction point shifts to Q4863. (D) Side chain orientation of critical residues in the S6 helices from neighboring subunits. The salt bridge between R4874 and E4872 is disrupted when the channel opens.

Figure 3.. 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 VSLcyt 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 VSLcyt domain are highlighted by red dashed ellipses. Locations are based on des Georges et al. (2016).