Extended Data Fig. 3: Structural analysis of TRPM5 with agonists calcium and CBTA.
From: A single allosteric site merges activation, modulation and inhibition in TRPM5
a, A close-up view of the CaTMD site of TRPM5 in the presence of EDTA (EMDB-23740). The atomic model is overlaid with cryo-EM map (PDB: 7MBP). b, A close-up view of the CaTMD site of the consensus map of EDTA/CBTA–TRPM5 dataset. The atomic model is overlaid with cryo-EM map. The CBTA density is clearly defined (yellow stick), whereas a weak CaTMD density is seen (green sphere). c, The close-up view of CaTMD (left panel) and CaICD (right panel) sites of the open state identified in CBTA/EDTA–TRPM5 dataset. The CaTMD density is strong whereas the CaICD is absent. d, The structural titration experiment of TRPM5 in the presence of various calcium concentrations (200 μM, 6 μM, 2 μM, and 1 μM). The upper and lower panels showed the close-up view of the CaTMD and CaICD sites, respectively. At 6 μM calcium concentration, two conformations of TRPM5 are identified, including one with both CaTMD and CaICD occupied, and another one in the apo state. e, Comparison of the CBTA-induced conformational change with the apo state and calcium-bound open state of TRPM5. The left panel indicates the S1–S4 domain, whereas right panel shows the S5–S6 pore domain. f, Structural comparison between CBTA/EGTA–TRPM5 (magenta) and Apo–TRPM5 (yellow). Residues surrounding CBTA are shown in stick representation. g, The cation-π stacking between CBTA, R834 and H837 in CBTA/EGTA–TRPM5 structure.
