4XDJ

Crystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1) in an alternate conformation (FORM 2)

4XDJ の概要

• エントリーDOI: 10.2210/pdb4xdj/pdb
• 関連するPDBエントリー: 4BW5
• 分子名称: POTASSIUM CHANNEL SUBFAMILY K MEMBER 10, POTASSIUM ION, 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (4 entities in total)
• 機能のキーワード: transport protein, outward rectification, membrane protein, k2p, structural genomics, structural genomics consortium, sgc
• 由来する生物種: homo sapiens (human)
• 細胞内の位置: Membrane ; Multi-pass membrane protein : P57789
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 128373.06

構造登録者

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) (登録日: 2014-12-19, 公開日: 2015-03-18, 最終更新日: 2024-10-16)

主引用文献

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

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: 25766236
DOI: 10.1126/science.1261512

実験手法

X-RAY DIFFRACTION (3.8 Å)