9JH1

The Cryo-EM structure of Kcnk13-S136P

9JH1 の概要

• エントリーDOI: 10.2210/pdb9jh1/pdb
• 関連するPDBエントリー: 9JGZ 9JH0
• EMDBエントリー: 61467 61468 61469
• 分子名称: Potassium channel subfamily K member 13, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, LINOLEIC ACID, ... (4 entities in total)
• 機能のキーワード: potassium channel, microglia function, cryo-em structure, neurodegenerative diseases, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66069.73

構造登録者

Xinagyun, F.,Haichao, J.,Jin, W.,Ran, Z.,Baobin, L. (登録日: 2024-09-08, 公開日: 2025-05-07, 最終更新日: 2025-07-30)

主引用文献

Fang, X.,Jin, H.,Wang, J.,Zhang, R.,Li, B.
Gating mechanism of the two-pore-domain potassium channel THIK1.
Nat.Struct.Mol.Biol., 32:1175-1182, 2025

PubMed Abstract: TWIK-related halothane-inhibited potassium channel (THIK1) maintains the resting membrane potential and regulates potassium efflux in microglia. It is a potential therapeutic target for neurodegenerative disorders, neuropathic pain and inflammation. However, the mechanism underlying its function remains unclear. Here we used cryo-electron microscopy to solve the structures of full-length human THIK1, revealing two inner gates and a C-type selectivity filter gate, distinct from other two-pore-domain potassium channels. One inner gate, formed by a short helix in the distal C terminus, introduces a unique gating mechanism involving the distal cytoplasmic domain. The other, beneath the selectivity filter, is constricted by Y273 in the M4 helix, dividing the cavity. In addition, the selectivity filter gate is modulated by polyunsaturated fatty acids. These structural insights into THIK1 gating, through the distal C-terminal helices, hydrophilic residues and selectivity filter, advance our understanding of THIK1's role in microglial homeostasis and neuropathologies.

PubMed: 40307591
DOI: 10.1038/s41594-025-01542-4

実験手法

ELECTRON MICROSCOPY (3.07 Å)