9JH1
The Cryo-EM structure of Kcnk13-S136P
Summary for 9JH1
| Entry DOI | 10.2210/pdb9jh1/pdb |
| Related | 9JGZ 9JH0 |
| EMDB information | 61467 61468 61469 |
| Descriptor | 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) |
| Functional Keywords | potassium channel, microglia function, cryo-em structure, neurodegenerative diseases, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 66069.73 |
| Authors | Xinagyun, F.,Haichao, J.,Jin, W.,Ran, Z.,Baobin, L. (deposition date: 2024-09-08, release date: 2025-05-07, Last modification date: 2025-05-14) |
| Primary citation | Fang, X.,Jin, H.,Wang, J.,Zhang, R.,Li, B. Gating mechanism of the two-pore-domain potassium channel THIK1. Nat.Struct.Mol.Biol., 2025 Cited by 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: 40307591DOI: 10.1038/s41594-025-01542-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.07 Å) |
Structure validation
Download full validation report
