Fig. 5: CBTA-mediated agonism does not require CaICD.
From: A single allosteric site merges activation, modulation and inhibition in TRPM5
a, Whole-cell recording of TRPM5-E337A elicited by various concentrations of CBTA. The pipette solution contained 5 mM EGTA. b, The dose–response curve and EC50 estimates of TRPM5-E337A to CBTA (n = 4). Circles represent the mean current and error bars represent the s.e.m. c, The pore profiles of apo TRPM5-E337A, Ca2+–TRPM5-E337A and CBTA/Ca2+–TRPM5-E337A. d, Structural comparison between CBTA/Ca2+–TRPM5(E337A) and Ca2+–TRPM5(E337A) (PDB 7MBU). The structures are shown in transparent cartoon representation, except for the TRP helix. CBTA is shown using yellow spheres. CBTA binding induced a motion of the TRP helix. e, The pore profiles of Ca2+–TRPM5-Q771A and CBTA/Ca2+–TRPM5-Q771A. f, The CaTMD site of CBTA/Ca2+–TRPM5-Q771A with the atomic model and cryo-EM density overlaid. The CBTA and CaTMD density is indicated. g, Bar graphs showing currents measured at +100 mV and −100 mV for Q771A (n = 4) and D797N (n = 4) mutants in the presence of 300 nM free calcium, without or with 1 μM CBTA.
