Structures of channelrhodopsin paralogs in peptidiscs explain their contrasting K+ and Na+ selectivities

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 () and Oliver P. Ernst ()
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Takefumi Morizumi: University of Toronto
Kyumhyuk Kim: University of Toronto
Hai Li: The University of Texas Health Science Center at Houston McGovern Medical School
Elena G. Govorunova: The University of Texas Health Science Center at Houston McGovern Medical School
Oleg A. Sineshchekov: The University of Texas Health Science Center at Houston McGovern Medical School
Yumei Wang: The University of Texas Health Science Center at Houston McGovern Medical School
Lei Zheng: The University of Texas Health Science Center at Houston McGovern Medical School
Éva Bertalan: RWTH-Aachen University
Ana-Nicoleta Bondar: University of Bucharest
Azam Askari: University of Guelph
Leonid S. Brown: University of Guelph
John L. Spudich: The University of Texas Health Science Center at Houston McGovern Medical School
Oliver P. Ernst: University of Toronto

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40041-2

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DOI: 10.1038/s41467-023-40041-2

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