Fig. 1: Potential menthol–TRPM8 interactions revealed by docking.
From: Molecular mechanisms underlying menthol binding and activation of TRPM8 ion channel
a The chemical structure of (−)-menthol, where its hydroxyl and isopropyl moieties are named as hand and legs, respectively. Menthol activated TRPM8 channel in a concentration-dependent manner in whole-cell patch-clamp recordings. b The concentration–response curve of menthol activation measured from whole-cell patch-clamp recordings (n = 5). c The maximum open probability (Po max) was determined from noise analysis of menthol-induced TRPM8 current. The measured maximum current (Imax_menthol) was normalized to the predicted maximum current to derive Po max. d The putative menthol-binding pocket located within the transmembrane domains of TRPM8 channel as revealed by cryo-EM. The zoom-in view of the binding pocket illustrated that residues known to be critical for menthol activation are tightly packed in the apo state (PDB ID: 6BPQ). e Docking of menthol into the binding pocket in the WS-12-bound activated state (PDB ID: 6NR2) lead to disruption of residue packing. The hydroxyl hand of menthol is predicted to form a hydrogen bond with the sidechain of R842 (dashed line in red). f–h Breakdown of the menthol-binding energy (h). The per-residue energy contributed by hydrogen bonding (f) and VDW interactions (g) was mapped onto the structure of TRPM8, respectively. The redder in color scale indicates larger energy value in REU (Rosetta energy unit). All statistical data are given as mean ± s.e.m. Source data are provided as a Source Data file.
