4XDK
Crystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1) in complex with norfluoxetine
Summary for 4XDK
| Entry DOI | 10.2210/pdb4xdk/pdb |
| Related | 4BW5 |
| Descriptor | Potassium channel subfamily K member 10, POTASSIUM ION, 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (5 entities in total) |
| Functional Keywords | transport protein, outward rectification, membrane protein, k2p, structural genomics, structural genomics consortium, sgc |
| Biological source | Homo sapiens (Human) |
| Cellular location | Membrane ; Multi-pass membrane protein : P57789 |
| Total number of polymer chains | 4 |
| Total formula weight | 129998.01 |
| Authors | Pike, A.C.W.,Dong, Y.Y.,Mackenzie, A.,Mukhopadhyay, S.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Burgess-Brown, N.A.,Carpenter, E.P.,Structural Genomics Consortium (SGC) (deposition date: 2014-12-19, release date: 2015-03-18, Last modification date: 2024-10-23) |
| Primary citation | Dong, Y.Y.,Pike, A.C.,Mackenzie, A.,McClenaghan, C.,Aryal, P.,Dong, L.,Quigley, A.,Grieben, M.,Goubin, S.,Mukhopadhyay, S.,Ruda, G.F.,Clausen, M.V.,Cao, L.,Brennan, P.E.,Burgess-Brown, N.A.,Sansom, M.S.,Tucker, S.J.,Carpenter, E.P. K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science, 347:1256-1259, 2015 Cited by PubMed 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. PubMed: 25766236DOI: 10.1126/science.1261512 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.6 Å) |
Structure validation
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