Figure 1.

Location of the disease-associated TRPM3 mutant residues

A: Top panel: Sequence alignment of the outer part of S6. The P1090/1092 residue in TRPM3 is highlighted blue. P1090 is the location of this residue in splice variant hTRPM3₁₃₂₅ used by both Zhao et al. [37] and Van Hoeymissen et al. [36] for functional studies, P1092 is the same reside in the hTRPM3α2 splice variant also used for functional studies by Zhao et al. [37]; they correspond to P937 in Dyment et al. [35]. Bottom panel: Sequence alignment of the S4-S5 loop, the V990/992 residue in TRPM3 is labeled red, V990 and V992 are the locations of the same residue in hTRPM3₁₃₂₅ and hTRPM3α2, and they both correspond to V837 in Dyment et al. [35].Yellow highlights indicate residues in contact with the agonists icilin and/or WS12 in the TRPM8 structures (6nr3, 6nr4, 6nr2), the residue highlighted green is in contact with PI[4,5]P₂ in TRPM8. B: the location of residues equivalent to V990/992 and P1090/1092 on the structure of TRPM4 (6bwi); one subunit is hidden for visibility. The short α-helical segment equivalent to the Gβγ binding site in TRPM3 is also shown. Adapted from Zhao et al. 2020 [37].