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Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs

View ORCID ProfileKyle Tucker, Savitha Sridharan, View ORCID ProfileHillel Adesnik, View ORCID ProfileStephen G. Brohawn
doi: https://doi.org/10.1101/2021.11.21.469454
Kyle Tucker
1Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, California 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720, USA
3California Institute for Quantitative Biology (QB3), University of California, Berkeley, CA 94720, USA
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Savitha Sridharan
1Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, California 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720, USA
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Hillel Adesnik
1Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, California 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720, USA
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  • For correspondence: hadesnik@berkeley.edu brohawn@berkeley.edu
Stephen G. Brohawn
1Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, California 94720, USA
2Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720, USA
3California Institute for Quantitative Biology (QB3), University of California, Berkeley, CA 94720, USA
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  • For correspondence: hadesnik@berkeley.edu brohawn@berkeley.edu
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Abstract

Microbial channelrhodopsins are light-gated ion channels widely used for optogenetic manipulation of neuronal activity. ChRmine is a bacteriorhodopsin-like cation channelrhodopsin (BCCR) more closely related to ion pump rhodopsins than other channelrhodopsins. ChRmine displays unique properties favorable for optogenetics including high light sensitivity, a red-shifted activation spectrum, cation selectivity, and large photocurrents while its slow closing kinetics impede some applications. The structural basis for ChRmine function, or that of any other BCCR, is unknown. Here, we present cryo-EM structures of ChRmine in lipid nanodiscs in apo (opsin) and retinal-bound (rhodopsin) forms. The structures reveal an unprecedented trimeric architecture with a lipid filled central pore. Large electronegative cavities on either side of the membrane facilitate high conductance and selectivity for cations over protons. The retinal binding pocket structure suggests spectral and kinetic properties could be tuned with mutations and we identify ChRmine variants with two-fold increased and ten-fold decreased closing rates. These results provide insight into structural features that generate an ultra-potent microbial opsin and provide a platform for rational engineering of channelrhodopsins with improved properties that could expand the scale, depth, and precision of optogenetic manipulations.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 22, 2021.
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Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs
Kyle Tucker, Savitha Sridharan, Hillel Adesnik, Stephen G. Brohawn
bioRxiv 2021.11.21.469454; doi: https://doi.org/10.1101/2021.11.21.469454
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Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs
Kyle Tucker, Savitha Sridharan, Hillel Adesnik, Stephen G. Brohawn
bioRxiv 2021.11.21.469454; doi: https://doi.org/10.1101/2021.11.21.469454

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