Viral Rhodopsins 1 Are an Unique Family of Light-gated Cation Channels

Phytoplankton is the base of the marine food chain as well as oxygen and carbon cycles and thus plays a global role in climate and ecology. Nucleocytoplasmic Large DNA Viruses that infect phytoplankton organisms and regulate the phytoplankton dynamics encompass genes of rhodopsins of two distinct families. Here, we present a functional and structural characterization of two proteins of viral rhodopsin group 1, OLPVR1 and VirChR1. Functional analysis of VirChR1 shows that it is a highly selective, Na/K-conducting channel and, in contrast to known cation channelrhodopsins, it is impermeable to Ca ions. We show that, upon illumination, VirChR1 is able to drive neural firing. The 1.4 Å resolution structure of OLPVR1 reveals remarkable differences from the known channelrhodopsins and a unique ion-conducting pathway. Thus, viral rhodopsins 1 represent a unique, large group of light-gated channels (viral channelrhodopsins, VirChR1s). In nature, VirChR1s likely mediate phototaxis of algae enhancing the host anabolic processes to support virus reproduction, and therefore, might play a major role in global phytoplankton dynamics. Moreover, VirChR1s have unique potential for optogenetics as they lack possibly noxious Ca permeability.

Citing Articles

Viral niche-partitioning: comparative genomics of giant viruses across environmental gradients in a high Arctic freshwater-saltwater lake.

Pitot T, Girard C, Rapp J, Somerville V, Culley A, Vincent W ISME Commun. 2025; 5(1):ycae155.

PMID: 39834781 PMC: 11745019. DOI: 10.1093/ismeco/ycae155.

Robust optogenetic inhibition with red-light-sensitive anion-conducting channelrhodopsins.

Oppermann J, Rozenberg A, Fabrin T, Gonzalez-Cabrera C, Parker R, Beja O Elife. 2024; 12.

PMID: 39401075 PMC: 11473104. DOI: 10.7554/eLife.90100.

Spatiotemporal dynamics of giant viruses within a deep freshwater lake reveal a distinct dark-water community.

Zhang L, Meng L, Fang Y, Ogata H, Okazaki Y ISME J. 2024; 18(1).

PMID: 39312489 PMC: 11465185. DOI: 10.1093/ismejo/wrae182.

Ocean to Tree: Leveraging Single-Molecule RNA-Seq to Repair Genome Gene Models and Improve Phylogenomic Analysis of Gene and Species Evolution.

Hsiao J, Deng L, Moroz L, Chalasani S, Edsinger E Methods Mol Biol. 2024; 2757:461-490.

PMID: 38668979 PMC: 11112408. DOI: 10.1007/978-1-0716-3642-8_19.

Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins.

Eria-Oliveira A, Folacci M, Chassot A, Fedou S, Theze N, Zabelskii D Nat Commun. 2024; 15(1):65.

PMID: 38167346 PMC: 10761956. DOI: 10.1038/s41467-023-44548-6.

References

Winn M, Ballard C, Cowtan K, Dodson E, Emsley P, Evans P . Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):235-42. PMC: 3069738. DOI: 10.1107/S0907444910045749. View

Yutin N, Koonin E . Proteorhodopsin genes in giant viruses. Biol Direct. 2012; 7:34. PMC: 3500653. DOI: 10.1186/1745-6150-7-34. View

Feldbauer K, Zimmermann D, Pintschovius V, Spitz J, Bamann C, Bamberg E . Channelrhodopsin-2 is a leaky proton pump. Proc Natl Acad Sci U S A. 2009; 106(30):12317-22. PMC: 2718366. DOI: 10.1073/pnas.0905852106. View

Wang Y, Wang F, Wang R, Zhao P, Xia Q . 2A self-cleaving peptide-based multi-gene expression system in the silkworm Bombyx mori. Sci Rep. 2015; 5:16273. PMC: 4633692. DOI: 10.1038/srep16273. View

Lopez J, Golemba M, Hernandez E, Lozada M, Dionisi H, Jansson J . Microbial and viral-like rhodopsins present in coastal marine sediments from four polar and subpolar regions. FEMS Microbiol Ecol. 2016; 93(1). DOI: 10.1093/femsec/fiw216. View

Li W, Godzik A . Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics. 2006; 22(13):1658-9. DOI: 10.1093/bioinformatics/btl158. View

Gushchin I, Shevchenko V, Polovinkin V, Kovalev K, Alekseev A, Round E . Crystal structure of a light-driven sodium pump. Nat Struct Mol Biol. 2015; 22(5):390-5. DOI: 10.1038/nsmb.3002. View

Vagin A, Teplyakov A . Molecular replacement with MOLREP. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 1):22-5. DOI: 10.1107/S0907444909042589. View

Jekely G . Evolution of phototaxis. Philos Trans R Soc Lond B Biol Sci. 2009; 364(1531):2795-808. PMC: 2781859. DOI: 10.1098/rstb.2009.0072. View

10.

Letunic I, Bork P . Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 2016; 44(W1):W242-5. PMC: 4987883. DOI: 10.1093/nar/gkw290. View

11.

Balashov S . Protonation reactions and their coupling in bacteriorhodopsin. Biochim Biophys Acta. 2000; 1460(1):75-94. DOI: 10.1016/s0005-2728(00)00131-6. View

12.

Short S . The ecology of viruses that infect eukaryotic algae. Environ Microbiol. 2012; 14(9):2253-71. DOI: 10.1111/j.1462-2920.2012.02706.x. View

13.

Govorunova E, Sineshchekov O, Janz R, Liu X, Spudich J . NEUROSCIENCE. Natural light-gated anion channels: A family of microbial rhodopsins for advanced optogenetics. Science. 2015; 349(6248):647-50. PMC: 4764398. DOI: 10.1126/science.aaa7484. View

14.

Murshudov G, Skubak P, Lebedev A, Pannu N, Steiner R, Nicholls R . REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):355-67. PMC: 3069751. DOI: 10.1107/S0907444911001314. View

15.

Berndt A, Lee S, Ramakrishnan C, Deisseroth K . Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science. 2014; 344(6182):420-4. PMC: 4096039. DOI: 10.1126/science.1252367. View

16.

Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P . Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A. 2003; 100(24):13940-5. PMC: 283525. DOI: 10.1073/pnas.1936192100. View

17.

Greiner T, Moroni A, Van Etten J, Thiel G . Genes for Membrane Transport Proteins: Not So Rare in Viruses. Viruses. 2018; 10(9). PMC: 6163359. DOI: 10.3390/v10090456. View

18.

Berndt A, Yizhar O, Gunaydin L, Hegemann P, Deisseroth K . Bi-stable neural state switches. Nat Neurosci. 2008; 12(2):229-34. DOI: 10.1038/nn.2247. View

19.

Kianianmomeni A, Stehfest K, Nematollahi G, Hegemann P, Hallmann A . Channelrhodopsins of Volvox carteri are photochromic proteins that are specifically expressed in somatic cells under control of light, temperature, and the sex inducer. Plant Physiol. 2009; 151(1):347-66. PMC: 2736010. DOI: 10.1104/pp.109.143297. View

20.

Li D, Liu C, Luo R, Sadakane K, Lam T . MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics. 2015; 31(10):1674-6. DOI: 10.1093/bioinformatics/btv033. View