Structures of thermo-sensitive TRP channels. (A) Two diagonally apposed TRPV1 subunits are shown in ribbon diagram, with regions proposed to undergo heat-evoked conformational changes highlighted with red. The phosphoinositide lipid predicted to be ejected from the vanilloid pocket upon heating is shown in sticks. (B) Comparison of structures of warm-activated TRPM2 and cold-activated TRPM8. Only the transmembrane region of one subunit is shown here. Unlike other TRP channels, TRPM8 lacks the helical S4–S5 linker and a structurally defined selectivity filter in a closed state, hinting at structural flexibility of these structural elements. PDB accession nos. are as follows: TRPV1 (5IRX), TRPM2 (6MIX), and TRPM8 (6BPQ).