Fig. 2: CBTA binds to the S1–S4 domain of TRPM5.
From: A single allosteric site merges activation, modulation and inhibition in TRPM5
a, The cryo-EM map of CBTA/EDTA–TRPM5. One subunit of TRPM5 is colored in blue. The CBTA density is shown in yellow. The MHR1/2 and MHR3/4 domains in TRPM5 are also indicated. b,c, The cryo-EM map (b) and atomic model (c) of CBTA/Ca2+–TRPM5. One subunit of TRPM5 is colored in red. The CBTA density is shown in yellow. CaTMD and CaICD in CBTA/Ca2+–TRPM5 are also indicated using green spheres. d, A close-up view of the CBTA-binding site. Residues that form the CBTA-binding pocket are shown in stick representation. The cryo-EM density corresponding to the CBTA molecule is shown using a semitransparent surface. e, The effect of 20 µM CBTA on whole-cell currents—recorded at −100 mV and +100 mV—in nontransfected tsA201 cells (n = 4), TRPM5 WT (n = 5) and TRPM5 mutants F730A, L764A, R834A, R998A and N723A (n = 4 each), with 5 mM EGTA included in the recording pipette, presented as bar graphs (mean). f, Pore profiles of the open states identified in the CBTA/EDTA–TRPM5 and Ca2+/EDTA–TRPM5 datasets, compared to those of the apo closed state and Ca2+-bound open state. g, The distribution of open and closed states in the presence of different calcium concentrations. The CaTMD and CaICD are allosterically coupled as we were unable to identify conformations of TRPM5 with only CaTMD or CaICD bound.
