Gating, Regulation, and Structure in K2P K+ Channels: In Varietate Concordia?
K2P K(+) channels with two pore domains in tandem associate as dimers to produce so-called background conductances that are regulated by a variety of stimuli. Whereas gating in K2P channels has been poorly understood, recent developments have provided important clues regarding the gating mechanism for this family of proteins. Two modes of gating present in other K(+) channels have been considered. The first is the so-called activation gating that occurs by bundle crossing and the splaying apart of pore-lining helices commanding ion passage. The second mode involves a change in conformation at the selectivity filter (SF), which impedes ion flow at this narrow portion of the conduction pathway and accounts for extracellular pH modulation of several K2P channels. Although some evidence supports the existence of an activation gate in K2P channels, recent results suggest that perhaps all stimuli, even those sensed at a distant location in the protein, are also mediated by SF gating. Recently resolved crystal structures of K2P channels in conductive and nonconductive conformations revealed that the nonconductive state is reached by blockade by a lipid acyl chain that gains access to the channel cavity through intramembrane fenestrations. Here we discuss whether this novel type of gating, proposed so far only for membrane tension gating, might mediate gating in response to other stimuli or whether SF gating is the only type of opening/closing mechanism present in K2P channels.
Centro de Estudios Científicos (CECs), Valdivia, Chile (M.I.N., L.P.C., F.V.S.), Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile (W.G.).
María Isabel
MI
Niemeyer
Centro de Estudios Científicos (CECs), Valdivia, Chile (M.I.N., L.P.C., F.V.S.), Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile (W.G.).
L Pablo
LP
Cid
Centro de Estudios Científicos (CECs), Valdivia, Chile (M.I.N., L.P.C., F.V.S.), Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile (W.G.).
Wendy
W
González
Centro de Estudios Científicos (CECs), Valdivia, Chile (M.I.N., L.P.C., F.V.S.), Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile (W.G.) fsepulveda@cecs.cl miniemeyer@cecs.cl.
Francisco V
FV
Sepúlveda
D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D040542:Mechanotransduction, Cellular; D008954:Models, Biological; D008958:Models, Molecular; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry* / Q000378:metabolism*
D024683:Potassium Channels, Tandem Pore Domain