4RUF: Human K2P4.1 (TRAAAK) potassium channel, W262S mutant

Mechanical and thermal activation of ion channels is central to touch, thermosensation, and pain. The TRAAK/TREK K(2P) potassium channel subfamily produces background currents that alter neuronal excitability in response to pressure, temperature, signaling lipids, and anesthetics. How such diverse stimuli control channel function is unclear. Here we report structures of K(2P)4.1 (TRAAK) bearing C-type gate-activating mutations that reveal a tilting and straightening of the M4 inner transmembrane helix and a buckling of the M2 transmembrane helix. These conformational changes move M4 in a direction opposite to that in classical potassium channel activation mechanisms and open a passage lateral to the pore that faces the lipid bilayer inner leaflet. Together, our findings uncover a unique aspect of K(2P) modulation, indicate a means for how the K(2P) C-terminal cytoplasmic domain affects the C-type gate which lies approximately 40A away, and suggest how lipids and bilayer inner leaflet deformations may gate the channel.
PDB ID: 4RUFDownload
MMDB ID: 125662
PDB Deposition Date: 2014/11/19
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 3.4  Å
Source Organism:
Similar Structures:
Biological Unit for 4RUF: dimeric; determined by author and by software (PISA)
Molecular Components in 4RUF
Label Count Molecule
Proteins (2 molecules)
Potassium Channel Subfamily K Member 4(Gene symbol: KCNK4)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB