4XDJ: Crystal Structure Of Human Two Pore Domain Potassium Ion Channel Trek2 (k2p10.1) In An Alternate Conformation (form 2)

Citation:
Abstract
TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.
PDB ID: 4XDJDownload
MMDB ID: 127941
PDB Deposition Date: 2014/12/19
Updated in MMDB: 2015/04
Experimental Method:
x-ray diffraction
Resolution: 3.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4XDJ: dimeric; determined by software (PISA)
Molecular Components in 4XDJ
Label Count Molecule
Proteins (2 molecules)
2
Potassium Channel Subfamily K Member 10(Gene symbol: KCNK10)
Molecule annotation
Chemicals (9 molecules)
1
3
2
4
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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