a, Backbone atom superposition of K2P2.1(TREK-1) (smudge, up), K2P2.1(TREK-1):ML335 (yellow, up), K2P2.1(TREK-1):ML402 (cyan, up), K2P10.1(TREK-2) (4BW5) (pink, up)6, K2P10.1(TREK-2) (4XDJ) (magenta, down)6, K2P10.1(TREK-2):Norfluoxetine (4XDK)(violet purple, down)6, K2P4.1(TRAAK) (4I9W) (limon, up)13, K2P4.1(TRAAK) G124I (4RUE) (marine, down)15, and K2P4.1(TRAAK) W262S (4RUF) (lime, down)15. ‘up’ or ‘down’ denotes M4 conformation. Selectivity filter ions for K2P2.1(TREK-1) (smudge), K2P2.1(TREK-1):ML335 (yellow), and K2P2.1(TREK-1):ML402 (cyan) are shown as spheres. ML335 and ML402 are shown in sticks. Select channel elements are labeled. b–e, Superposition showing b, K2P2.1(TREK-1) chain A (smudge) and chain B (light orange). Sites of GOF mutations, G137I (orange)7, and Trp2758, are indicated. c, K2P2.1(TREK-1):ML335 chain A (pink) and chain B (deep salmon), d, K2P2.1(TREK-1):ML402 chain A (cyan) and chain B (deep teal). e, K2P2.1(TREK-1) chain A (smudge) and chain B (light orange), K2P10.1(TREK-2) (4BW5) (pink)6, K2P10.1(TREK-2) (4XDJ) (magenta)6, K2P10.1(TREK-2):Norfluoxetine (4XDK)(violet purple)6. f, K2P2.1(TREK-1):ML335 (deep salmon), K2P4.1(TRAAK) (4I9W) (limon)13, K2P4.1(TRAAK) G124I (4RUE) (marine)15, K2P4.1(TRAAK) W262S (4RUF) (lime)15. G124I from K2P4.1(TRAAK) G124I15 is shown in sticks. In b–f, Phe134, His126, Lys271, Trp275, their equivalents in K2P10.1(TREK-2), K2P4.1(TRAAK), and K2P4.1(TRAAK) G124I, are shown in sticks. ML335, ‘c’, and ML402, ‘d’, are shown as sticks.