Extended Data Fig. 7: TMD-ICD coupling in TRPM5.

a and b, A close up view of the Ca_TMD (a) site and Ca_ICD (b) site of CBTA/Ca²⁺–TRPM5(E337A) structure. The cryo-EM map is overlaid with atomic model with relevant residues shown in stick representation. The CBTA and Ca_TMD density are well defined, whereas Ca_ICD is absent. c, A close-up view of the Ca_TMD (left panel) and Ca_ICD (right panel) sites of Ca²⁺–TRPM5(Q771A) dataset. d, Subunit comparison of the EDTA/CBTA–TRPM5(WT) and CBTA/Ca²⁺–TRPM5(E337A) with the apo and open state of TRPM5. The root-mean-square-deviation (RMSD) of the intracellular domain (ICD) of the structures relative to the apo and open state is shown in the inlet. Both CBTA/EGTA–TRPM5(WT) and the CBTA/Ca²⁺–TRPM5(E337A) adopts an intermediate conformation between apo and open state. e, Comparison of the S1–S4 domain between Apo–TRPM5 and Ca²⁺–TRPM5 (left panel), and Ca²⁺–TRPM5(Q771A) and Apo–TRPM5(WT) (right panel). f, Comparison of the ICD of Ca²⁺–TRPM5(Q771A) with Apo–TRPM5 and Ca²⁺–TRPM5. The ICD of Ca²⁺–TRPM5(Q771A) adopts an intermediate conformation. g, Subunit-focused analysis identified classes with Ca_ICD-bound (left panel) and -unbound (right panel) states for Ca²⁺–TRPM5(Q771A). h, Cryo-EM map comparison of the MHR1/2 domain between the Ca_ICD-bound (cyan) and -unbound (magenta) subunits for the Ca²⁺–TRPM5(Q771A). h, Comparison of Ca²⁺/CBTA–TRPM5(Q771A) with the open state of TRPM5. i, The Ca_ICD of Ca²⁺/CBTA–TRPM5(Q771A) is fully occupied, distinct from Ca²⁺–TRPM5(Q771A) as seen in (g). j, The Ca_ICD of Ca²⁺/CBTA–TRPM5(Q771A) is fully occupied, distinct from the Ca_ICD of Ca²⁺–TRPM5(Q771A) as seen in g.