Extended Data Figure 9. Lipid co-factor and vanilloids at the vanilloid binding site of TRPV1.

a, Chemical structure of phosphatidylinositol. b, Local environment of the phosphatidylinositol binding site may accommodate multiple phosphatidylinositide species with phosphate substituents at 3, 4 and/or 5 positions of the inositol ring (drawn in red). Adjacent regions of the channel are shown as ribbon diagram (grey). c, Tyr511 assumes two possible orientations that differ in apo versus agonist-bound states of the TRPV1 channel. In the apo state, one acyl chain of the resident phosphatidylinositol lipid (blue mesh superimposed with atomic model) prevents the Tyr511 side chain from assuming the upward rotamer position. d, Density maps of vanilloids (resiniferatoxin, red mesh; capsazepine, gold mesh) superimposed with density of the bound phosphatidylinositol lipid (blue mesh), suggesting that they occupy overlapping, but not identical sites. Atomic models for both drugs and their chemical structures are also shown. e, Overlap of transmembrane region of one TRPV1 subunit corresponding to apo (blue) and RTX/DkTx-bound (orange) states. Note the relatively small conformational change of the voltage sensor-like domain (S1–S4, boxed region). f, Overlap of transmembrane region of one TRPV1 subunit corresponding to apo (blue) and capsazepine-bound (gold) states.