Extended Data Fig. 5: K2P13.1(THIK-1) structural and sequence features. | Nature Structural & Molecular Biology

Extended Data Fig. 5: K2P13.1(THIK-1) structural and sequence features.

From: Structure of the human K2P13.1 channel reveals a hydrophilic pore restriction and lipid cofactor site

Extended Data Fig. 5

a, Cytoplasmic view of the K2P13.1(THIK-1) Asn ring (Asn134 and Asn227) and flow restrictor barrier (Ile139 and Tyr273). Ser136 is also shown. Linoleic acid (EIC) is shown in space filling. b, Lateral view of the K2P13.1(THIK-1) central cavity. Asn ring (Asn134 and Asn227) and flow restrictor barrier (Ile139 and Tyr273) are labeled. EIC and S4 potassium ion (violet) are shown in space filling. Pond and inner vestibule regions are shown in blue. c, M4 sequence comparison. Labels indicate: K2P13.1(THIK-1) EIC contact residues (orange), flow restrictor (red), Asn ring (green), and K2P2.1(TREK-1) K2P modulator pocket residues that contact the ML335 activator (light blue)24. Black asterisk denotes Arg sandwich residue. d, M2 sequence comparison. Labels indicate K2P13.1(THIK-1) EIC contact residues (orange) and Asn ring (green). Red ‡ indicates S136P mutation site. e, PUFA site showing hydrogen bond and salt bridge interactions (dashed lines) and van der Waals contacts ≤ 5 Å. Colors indicate residues from the M1 (teal), M2 (magenta), P1 (salmon), and M4 (violet) helices. EIC is yelloworange and black. f, P1 sequence comparison. Labels indicate K2P13.1(THIK-1) EIC contact residues (orange) and K2P2.1(TREK-1) K2P modulator pocket residues that contact the ML335 activator (light blue)24. Black asterisk denotes Arg sandwich residue. g, M1 sequence comparison. Labels indicate K2P13.1(THIK-1) EIC contact residues (orange). h, Superposition of the SF1-M2 regions of K2P13.1(THIK-1) (salmon), K2P13.1(THIK-1) S136P (cyan), and K2P13.1(THIK-1) S136P/Y273A (magenta) with K2P2.1(TREK-1):ML335 (light blue) (PDB:6CQ6)24, K2P10.1(TREK-2):norfluoxetine (Nfx) (hot pink) (PDB:4XDK)29, K2P5.1(TASK-2) pH 6.5 (orange) (PDB:6WLV)32 and pH 8.5 (teal) (PDB:6WM0)32, K2P1.1(TWIK-1) (deep olive) (PDB:3UKM)30, pH 7.4 (7SK0)31, and pH 5.5 (7SK1)31, and K2P3.1(TASK-1) (grey) (PDB:6RV2)33. Cyan lines show the range of M2 movements indicated by the 15° double headed arc. Potassium ions are shown as purple spheres. GenBank Sequences in c, d, f, and g are for human: K2P13.1(THIK-1) 16306555; K2P13.2(THIK-2) 11545761; K2P2.1(TREK-1) 14589851; K2P10.1(TREK-2) 20143944; K2P4.1(TRAAK) 15718767; K2P3.1(TASK-1) 4504849; K2P9.1 (TASK-3) 542133161; K2P15.1(TASK-5) 333440483; K2P5.1(TASK-2) 333440483; K2P16.1(TALK-1) 14149764; K2P17.1(TALK-2) 17025230; K2P1.1(TWIK-1) 4504847; K2P6.1(TWIK-2) 4758624; and K2P18.1(TRESK) 32469495.

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