The membrane-bound state of K2P potassium channels.
Potassium channel subunits composed of two-pore domains arranged in tandem (K(2P)) are of paramount importance for neural function. A variety of stimuli, such as membrane depolarization and tension, acidification, and anesthetic action, activate K(2P) channels. Most of the channel sensitivity is attributed to its intracellular C-terminal moiety, which works as a sensor domain required for proper integration of the electrical, chemical, and mechanical signals into channel activity. Herein, the structure of K(2P) in a membrane environment has been studied using molecular dynamics (MD). Two distinct fully atomistic models for the most studied K(2P) channel, namely, the TWIK-related (TREK)-1 channel have been built. These constructs were then inserted into a fully hydrated zwitterionic lipid bilayer, and each relaxed by means of MD simulations spanning approximately 0.3 micros. Both simulated TREK-1 structures converged to a final conformation characterized by a closed pore and a C-terminal domain adsorbed onto the lipid bilayer surface. The C-terminus, which is physically linked to the pore and energetically coupled to the bilayer, is poised to gate the channel in response to membrane stimulation. The present study indicates the nature of the direct coupling between the C-terminal domain and the membrane, which is a key structural feature underlying K(2P) channel function.
Treptow
Werner
W
Laboratório de Biofísica, Departamento de Biologia Celular, Universidade de Brasília, Brasília, Brasil. treptow@unb.br
Klein
Michael L
ML
D016718:Arachidonic Acid / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D055595:Mechanical Phenomena; D056004:Molecular Dynamics Simulation; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary
D008051:Lipid Bilayers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D016718:Arachidonic Acid