9C07

Structure of K2P13.1 (THIK1) S136P in detergent

Summary for 9C07

• Entry DOI: 10.2210/pdb9c07/pdb
• Related: 9BSN
• EMDB information: 44870 45075
• Descriptor: Potassium channel subfamily K member 13, DODECANE, N-OCTANE, ... (7 entities in total)
• Functional Keywords: potassium channel, k2p channel, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 83079.68

Authors

Roy-Chowdhury, S.,Adberemane-Ali, F.,Minor, D.L. (deposition date: 2024-05-24, release date: 2025-02-26, Last modification date: 2025-05-14)

Primary citation

Roy-Chowdhury, S.,Jang, S.,Abderemane-Ali, F.,Naughton, F.,Grabe, M.,Minor Jr., D.L.
Structure of the human K 2P 13.1 channel reveals a hydrophilic pore restriction and lipid cofactor site.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Polyunsaturated fatty acid (PUFA) lipids modulate the neuronal and microglial leak potassium channel K13.1 (THIK1) and other voltage-gated ion channel (VGIC) superfamily members through poorly understood mechanisms. Here we present cryo-electron microscopy structures of human THIK1 and mutants, revealing a unique two-chamber aqueous inner cavity obstructed by a hydrophilic barrier important for gating, the flow restrictor, and a P1-M4 intersubunit interface lipid at a site, the PUFA site, corresponding to the K small-molecule modulator pocket. This overlap, together with functional studies, indicates that PUFA site lipids are THIK1 cofactors. Comparison with a PUFA-responsive VGIC, K7.1, reveals a shared modulatory role for the pore domain intersubunit interface, providing a framework for understanding PUFA action on the VGIC superfamily. Our findings reveal the distinct THIK1 architecture, highlight the importance of the P1-M4 interface for K control by natural and synthetic ligands and should aid in the development of THIK subfamily modulators for neuroinflammation and autism.

PubMed: 40011746
DOI: 10.1038/s41594-024-01476-3

Experimental method

ELECTRON MICROSCOPY (2.73 Å)