Figure 1.

RyR1 architecture and domain organization. 3D conformation of RyR1 + ATP/Caf/Ca²⁺ (open) (Protein Data Bank: 5TAL) with Ca²⁺-, ATP-, and Caf-binding sites. Two of four chains shown depict the activation core and ligand sites. The color code of individual domains is as follows: cytosolic shell (light blue), S2S3 domain (cyan), TaF domain (orange), S6c-pore helix (green), pore domain (magenta), TMD (yellow), and CTD (black). Binding sites for Ca²⁺ (green), ATP (blue), and Caf (red) are enlarged to show specific interactions for each ligand. The activation ligands are in the activation core and at the interfaces of CTD, CSol, S2S3, TaF, and S6c domains. Caf, caffeine; CMD, COOH-terminal membrane-anchoring domain; CSol, core α-solenoid domain; CTD, C-terminal domain; RyR1, ryanodine receptor type 1; TMD, transmembrane domain.