Extended Data Figure 8. Structural comparison of the RyR1 channel domain with representative tetrameric cation channels of known structures.

a, Structural comparison of the pore forming elements from different tetrameric cation channels of known structures. Two diagonal protomers are shown. In all the structures, the S5 and S6 segments are colored grey. In the structures of Ca_vAb and KcsA, the bound ions are shown as spheres. PDB accession codes: 4MW3 for Ca_vAb, 3J5Q for TRPV1, and 1BL8 for KcsA. b, Structural comparison of the transmembrane region of RyR1-VSL to the VSDs or like domains in the indicated tetrameric ion channels. Note that a hydrophilic sequence between S1 and S2 (residues 4579-4639) exhibits poor EM density and constitutes the least conserved DR1 region (DR for “divergent”) in the RyR1 channel domain¹¹ (Extended Data Fig. 7). The ordered segments within this sequence form a pair of short anti-parallel β-strands that extends into the SR lumen. PDB accession codes: 2R9R for the Kv1.2/Kv2.1 paddle chimera, 4DXW for Na_vRh, and 3J5P for TRPV1.