K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac

@article{Dong2015K2PCG,
  title={K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac},
  author={Yin Yao Dong and Ashley C W Pike and Alexandra Mackenzie and Conor McClenaghan and Prafulla Aryal and Liang Dong and Andrew Quigley and Mariana Grieben and Solenne Goubin and Shubhashish Mukhopadhyay and Gian Filippo Ruda and Michael V. Clausen and Lishuang Cao and Paul E Brennan and Nicola A. Burgess-Brown and Mark S. P. Sansom and Stephen J Tucker and Elisabeth P Carpenter},
  journal={Science},
  year={2015},
  volume={347},
  pages={1256-1259}
}
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… CONTINUE READING