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-Structure paper
タイトル | Structures of channelrhodopsin paralogs in peptidiscs explain their contrasting K and Na selectivities. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 4365, Year 2023 |
掲載日 | 2023年7月20日 |
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 / |
PubMed 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. |
リンク | Nat Commun / PubMed:37474513 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.84 - 2.88 Å |
構造データ | EMDB-40062, PDB-8gi8: EMDB-40063, PDB-8gi9: |
化合物 | ChemComp-RET: ChemComp-NA: ChemComp-CLR: ChemComp-PEE: ChemComp-HOH: |
由来 |
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キーワード | TRANSPORT PROTEIN / Retinal Protein / Channelrhodopsin / Cation channel / Peptidisc / Optogenetics |