Extended Data Fig. 9: Models for representative cavity between the orthosteric pocket and allosteric site in TAS2R14.

a, Representative orthosteric and allosteric site of TAS2R14. The pockets are occupied by cholesterol and cmpd28.1 shown as spheres. b, A model for electrostatic potential surface showing the orthosteric binding pocket engaged by cholesterol of TAS2R14. Red, negative (−5 kT e⁻¹); blue, positive (+5 kT e⁻¹). c, Extensive aromatic residues which are abundant in TM5 and TM6 form a hydrophobic network along with the cavity. The network interacts with cholesterol and cmpd28.1. d–h, Orthogonal views for representative models for TAS2R14–G_i1 with the deep and elongated cavity which was predicted using Caver 3.0.3 software⁶³. The cavity was colored orange. A predicted tunnel for the entrance of cholesterol is indicated by red circles (e–f,h). g, Close-up view of the predicted entrance from d. Surrounding residues are shown as sticks. i-k, Cavities predicted by Caver 3.0.3⁶³ in SMO receptor (PDB 6O3C) (i), GPBAR (PDB 7CFN) (j), and TAS2R46 (PDB 7XP6) (k). The calculated cavities were colored green (i-k).