Natural Sciences and Engineering Research Council (NSERC, Canada)
RGPIN-2018-04397
カナダ
Natural Sciences and Engineering Research Council (NSERC, Canada)
RGPIN-2017-06862
カナダ
Canadian Institutes of Health Research (CIHR)
PJT-159464
カナダ
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Structures of channelrhodopsin paralogs in peptidiscs explain their contrasting K and Na selectivities. 著者: Takefumi Morizumi / Kyumhyuk Kim / Hai Li / Elena G Govorunova / Oleg A Sineshchekov / Yumei Wang / Lei Zheng / Éva Bertalan / Ana-Nicoleta Bondar / Azam Askari / Leonid S Brown / John L ...著者: Takefumi Morizumi / Kyumhyuk Kim / Hai Li / Elena G Govorunova / Oleg A Sineshchekov / Yumei Wang / Lei Zheng / Éva Bertalan / Ana-Nicoleta Bondar / Azam Askari / Leonid S Brown / John L Spudich / Oliver P Ernst / 要旨: Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is a light-gated channel used for optogenetic silencing of mammalian neurons. It selects K over Na in the absence of the canonical ...Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is a light-gated channel used for optogenetic silencing of mammalian neurons. It selects K over Na in the absence of the canonical tetrameric K selectivity filter found universally in voltage- and ligand-gated channels. The genome of H. catenoides also encodes a highly homologous cation channelrhodopsin (HcCCR), a Na channel with >100-fold larger Na to K permeability ratio. Here, we use cryo-electron microscopy to determine atomic structures of these two channels embedded in peptidiscs to elucidate structural foundations of their dramatically different cation selectivity. Together with structure-guided mutagenesis, we show that K versus Na selectivity is determined at two distinct sites on the putative ion conduction pathway: in a patch of critical residues in the intracellular segment (Leu69/Phe69, Ile73/Ser73 and Asp116) and within a cluster of aromatic residues in the extracellular segment (primarily, Trp102 and Tyr222). The two filters are on the opposite sides of the photoactive site involved in channel gating.