Structural elements that confer conformational flexibility to the pore lining S6 helix in K⁺ and TRPV1 channels. (A) Gating hinges in KcsA (Gly99; red) and K_v2.1 (Pro-Val-Pro; shown in sticks) allow for splaying open of their activation gates. (B) A π-helix bulge, highlighted in sticks, likely provides a flexing point around which the distal S6 helix can rotate and/or bend to open the lower gate in TRPV1. PDB accession nos. are as follows: KcsA (5VKE), Kv2.1 (2R9R), and TRPV1 (3J5R).