Extended Data Fig. 6: Comparison of NvTRPM2 with DrTRPM2 (EDTA–TRPM2 and ADPR/Ca²⁺–TRPM2) and HsTRPM4, and comparison of the gate and selectivity filter of EDTA–TRPM2 with those of HsTRPM4 (PDB: 5WP6).

a–c, Superimposition of EDTA–TRPM2 (a, blue, r.m.s.d = 50 Å, overall, main chain atoms only), ADPR/Ca²⁺–TRPM2 (b, red, r.m.s.d = 50 Å, overall, main chain atoms only) and HsTRPM4 (c, green, r.m.s.d = 47.5 Å, overall, main chain atoms only) with NvTRPM2 (yellow). The NUDT9-H domain is completely invisible in NvTRPM2. d–f, Superimposition of the MHR1/2 domains of EDTA–TRPM2 (d, blue), ADPR/Ca²⁺–TRPM2 (e, red) and HsTRPM4 (f, green) with NvTRPM2 (yellow). g–i, Superimposition of the transmembrane domains of EDTA–TRPM2 (g, blue), ADPR/Ca²⁺–TRPM2 (h, red) and HsTRPM4 (i, green) with NvTRPM2 (yellow). The transmembrane domain of NvTRPM2 is distinct from EDTA–TRPM2 and ADPR/Ca²⁺–TRPM2 but very similar to that of HsTRPM4. j, k, Comparison of the gates of TRPM2 (blue) and TRPM4 (green) viewed from the intracellular side of the membrane (j), or viewed parallel to the membrane (k). Only two subunits are shown in (k) for clarity. l, m, Comparison of the selectivity filters of DrTRPM2 and HsTRPM4 viewed from the extracellular side of the membrane (l), or viewed parallel to the membrane (m). Only two subunits are shown in m for clarity. The superimposition was performed by aligning the P loop and S6 (residues 958–1050 in HsTRPM4 and residues 978–1069 in DrTRPM2). The Cα atoms of the residues in the selectivity filter and gate are shown as spheres.