Figure 3

Schematic diagram of RYR1 protein subunit and pathogenic variants in this study. RYR1 is a homotetramer with each subunit consisting of a large cytoplasmic moiety and a transmembrane domain. This figure depicts one subunit of the RYR1 protein. The cytoplasmic moiety contains (1) the N-terminal domain (NTD) with 3 subdomains (A, B, C), (2) 3 SPRY domains (SPRY 1, 2, 3), of which SPRY 2 and 3 interact with the α1 subunit of DHPR at the II-III loop region, (3) a solenoid region comprising the handle/ junctional solenoid (J-sol) domain, and the helical (HD1, HD2)/ bridging solenoid (B-Sol) domains, (4) 2 tandem repeat domains (R1&2, R3&4), and (5) a Central domain or core solenoid (C-Sol). The transmembrane domain consists of 6 transmembrane helices (S1–6), and a C-terminal domain (CTD). S5 and 6, together with a pore helix in between S5 and S6, make up the pore-forming region (PF)^19,25,34. The amino acid residue numbers for the various domains have been labelled, and the pathogenic RYR1 mutations are indicated at their various positions across the protein.