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Structure–Function Relationship of Channelrhodopsins

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Book cover Optogenetics

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1293))

Abstract

Ion-translocating rhodopsins, especially channelrhodopsins (ChRs), have attracted broad attention as a powerful tool to modulate the membrane potential of cells with light (optogenetics). Because of recent biophysical, spectroscopic, and computational studies, including the structural determination of cation and anion ChRs, our understanding of the molecular mechanism underlying light-gated ion conduction has been greatly advanced. In this chapter, I first describe the background of rhodopsin family proteins including ChR, and how the optogenetics technology has been established from the discovery of first ChR in 2002. I later introduce the recent findings of the structure–function relationship of ChR by comparing the crystal structures of cation and anion ChRs. I further discuss the future goal in the fields of ChR research and optogenetic tool development.

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Abbreviations

7TM:

Seven transmembrane

ACR:

Anion-conducting channelrhodopsin

ATR:

All-trans-retinal

CCR:

Cation-conducting channelrhodopsin

CrChR2 (or ChR2):

Cation channelrhodopsin-2 from Chlamydomonas reinhardtii

dACR:

Designed anion-conducting channelrhodopsin

GPCR:

G protein-coupled receptor

HR:

Halorhodopsins

HsBR:

Bacteriorhodopsin from Halobacterium salinarum

MD simulation:

Molecular dynamics simulation

nACR:

Natural anion-conducting channelrhodopsin

NpHR:

Halorhodopsin from Natronomonas pharaonis

TR-SFX:

Time-resolved serial femtosecond crystallography

TR-SMX:

Time-resolved serial millisecond crystallography

References

  • Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L (2007) Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450:420–424

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ardevol A, Hummer G (2018) Retinal isomerization and water-pore formation in channelrhodopsin-2. Proc Natl Acad Sci U S A 115:3557–3562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bamann C, Gueta R, Kleinlogel S, Nagel G, Bamberg E (2010) Structural guidance of the photocycle of channelrhodopsin-2 by an interhelical hydrogen bond. Biochemistry (Mosc) 49:267–278

    Article  CAS  Google Scholar 

  • Berndt A, Yizhar O, Gunaydin LA, Hegemann P, Deisseroth K (2009) Bi-stable neural state switches. Nat Neurosci 12:229–234

    Article  CAS  PubMed  Google Scholar 

  • Berndt A, Schoenenberger P, Mattis J, Tye KM, Deisseroth K, Hegemann P, Oertner TG (2011) High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels. Proc Natl Acad Sci U S A 108:7595–7600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berndt A, Lee SY, Ramakrishnan C, Deisseroth K (2014) Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science 344:420–424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berndt A, Lee SY, Wietek J, Ramakrishnan C, Steinberg EE, Rashid AJ, Kim H, Park S, Santoro A, Frankland PW et al (2016) Structural foundations of optogenetics: determinants of channelrhodopsin ion selectivity. Proc Natl Acad Sci U S A 113:822–829

    Article  CAS  PubMed  Google Scholar 

  • Berthold P, Tsunoda SP, Ernst OP, Mages W, Gradmann D, Hegemann P (2008) Channelrhodopsin-1 initiates phototaxis and photophobic responses in chlamydomonas by immediate light-induced depolarization. Plant Cell 20:1665–1677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, Pan ZH (2006) Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50:23–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bogomolni RA, Spudich JL (1982) Identification of a third rhodopsin-like pigment in phototactic Halobacterium halobium. Proc Natl Acad Sci U S A 79:6250–6254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268

    CAS  PubMed  Google Scholar 

  • Cheng C, Kamiya M, Takemoto M, Ishitani R, Nureki O, Yoshida N, Hayashi S (2018) An atomistic model of a precursor state of light-induced channel opening of Channelrhodopsin. Biophys J 115:1281–1291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho YK, Park D, Yang A, Chen F, Chuong AS, Klapoetke NC, Boyden ES (2019) Multidimensional screening yields channelrhodopsin variants having improved photocurrent and order-of-magnitude reductions in calcium and proton currents. J Biol Chem 294:3806–3821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE et al (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463:98–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chuong AS, Miri ML, Busskamp V, Matthews GA, Acker LC, Sorensen AT, Young A, Klapoetke NC, Henninger MA, Kodandaramaiah SB et al (2014) Noninvasive optical inhibition with a red-shifted microbial rhodopsin. Nat Neurosci 17:1123–1129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dawydow A, Gueta R, Ljaschenko D, Ullrich S, Hermann M, Ehmann N, Gao S, Fiala A, Langenhan T, Nagel G et al (2014) Channelrhodopsin-2-XXL, a powerful optogenetic tool for low-light applications. Proc Natl Acad Sci U S A 111:13972–13977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deisseroth K (2011) Optogenetics. Nat Methods 8:26–29

    Article  CAS  PubMed  Google Scholar 

  • Deisseroth K (2015) Optogenetics: 10 years of microbial opsins in neuroscience. Nat Neurosci 18:1213–1225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duan X, Nagel G, Gao S (2019) Mutated channelrhodopsins with increased sodium and calcium permeability. Appl Sci 9:664

    Article  CAS  Google Scholar 

  • Ernst OP, Lodowski DT, Elstner M, Hegemann P, Brown LS, Kandori H (2014) Microbial and animal rhodopsins: structures, functions, and molecular mechanisms. Chem Rev 114:126–163

    Article  CAS  PubMed  Google Scholar 

  • Gaiko O, Dempski RE (2013) Transmembrane domain three contributes to the ion conductance pathway of channelrhodopsin-2. Biophys J 104:1230–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Govorunova EG, Sineshchekov OA, Li H, Janz R, Spudich JL (2013) Characterization of a highly efficient blue-shifted channelrhodopsin from the marine alga Platymonas subcordiformis. J Biol Chem 288:29911–29922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Govorunova EG, Sineshchekov OA, Janz R, Liu X, Spudich JL (2015) Neuroscience. Natural light-gated anion channels: a family of microbial rhodopsins for advanced optogenetics. Science 349:647–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Govorunova EG, Sineshchekov OA, Spudich JL (2016) Structurally distinct cation Channelrhodopsins from Cryptophyte algae. Biophys J 110:2302–2304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Govorunova EG, Sineshchekov OA, Rodarte EM, Janz R, Morelle O, Melkonian M, Wong GK, Spudich JL (2017) The expanding family of natural anion Channelrhodopsins reveals large variations in kinetics, conductance, and spectral sensitivity. Sci Rep 7:43358

    Article  PubMed  PubMed Central  Google Scholar 

  • Govorunova EG, Sineshchekov OA, Hemmati R, Janz R, Morelle O, Melkonian M, Wong GK, Spudich JL (2018) Extending the time domain of neuronal silencing with Cryptophyte anion Channelrhodopsins. eNeuro 5:ENEURO.0174

    Article  Google Scholar 

  • Govorunova EG, Sineshchekov OA, Li H, Wang Y, Brown LS, Spudich JL (2020) RubyACRs, nonalgal anion channelrhodopsins with highly red-shifted absorption. Proc Natl Acad Sci U S A 117:22833–22840

    Google Scholar 

  • Gunaydin LA, Yizhar O, Berndt A, Sohal VS, Deisseroth K, Hegemann P (2010) Ultrafast optogenetic control. Nat Neurosci 13:387–392

    Article  CAS  PubMed  Google Scholar 

  • Han X, Boyden ES (2007) Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One 2:e299

    Article  PubMed  PubMed Central  Google Scholar 

  • Harz H, Hegemann P (1991) Rhodopsin-regulated calcium currents in Chlamydomonas. Nature 351:489–491

    Article  CAS  Google Scholar 

  • Hegemann P (2008) Algal sensory photoreceptors. Annu Rev Plant Biol 59:167–189

    Article  CAS  PubMed  Google Scholar 

  • Hirai T, Subramaniam S, Lanyi JK (2009) Structural snapshots of conformational changes in a seven-helix membrane protein: lessons from bacteriorhodopsin. Curr Opin Struct Biol 19:433–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hochbaum DR, Zhao Y, Farhi SL, Klapoetke N, Werley CA, Kapoor V, Zou P, Kralj JM, Maclaurin D, Smedemark-Margulies N et al (2014) All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat Methods 11:825–833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou SY, Govorunova EG, Ntefidou M, Lane CE, Spudich EN, Sineshchekov OA, Spudich JL (2012) Diversity of Chlamydomonas channelrhodopsins. Photochem Photobiol 88:119–128

    Article  CAS  PubMed  Google Scholar 

  • Inaguma A, Tsukamoto H, Kato HE, Kimura T, Ishizuka T, Oishi S, Yawo H, Nureki O, Furutani Y (2015) Chimeras of channelrhodopsin-1 and -2 from Chlamydomonas reinhardtii exhibit distinctive light-induced structural changes from channelrhodopsin-2. J Biol Chem 290:11623–11634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue K, Ono H, Abe-Yoshizumi R, Yoshizawa S, Ito H, Kogure K, Kandori H (2013) A light-driven sodium ion pump in marine bacteria. Nat Commun 4:1678

    Article  PubMed  CAS  Google Scholar 

  • Inoue K, Ito S, Kato Y, Nomura Y, Shibata M, Uchihashi T, Tsunoda SP, Kandori H (2016) A natural light-driven inward proton pump. Nat Commun 7:13415

    Article  PubMed  PubMed Central  Google Scholar 

  • Ishizuka T, Kakuda M, Araki R, Yawo H (2006) Kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels. Neurosci Res 54:85–94

    Article  CAS  PubMed  Google Scholar 

  • Kato HE, Zhang F, Yizhar O, Ramakrishnan C, Nishizawa T, Hirata K, Ito J, Aita Y, Tsukazaki T, Hayashi S et al (2012) Crystal structure of the channelrhodopsin light-gated cation channel. Nature 482:369–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato HE, Kamiya M, Sugo S, Ito J, Taniguchi R, Orito A, Hirata K, Inutsuka A, Yamanaka A, Maturana AD et al (2015) Atomistic design of microbial opsin-based blue-shifted optogenetics tools. Nat Commun 6:7177

    Article  CAS  PubMed  Google Scholar 

  • Kato HE, Kim YS, Paggi JM, Evans KE, Allen WE, Richardson C, Inoue K, Ito S, Ramakrishnan C, Fenno LE et al (2018) Structural mechanisms of selectivity and gating in anion channelrhodopsins. Nature 561:349–354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim YS, Kato HE, Yamashita K, Ito S, Inoue K, Ramakrishnan C, Fenno LE, Evans KE, Paggi JM, Dror RO et al (2018) Crystal structure of the natural anion-conducting channelrhodopsin GtACR1. Nature 561:343–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klapoetke NC, Murata Y, Kim SS, Pulver SR, Birdsey-Benson A, Cho YK, Morimoto TK, Chuong AS, Carpenter EJ, Tian Z et al (2014) Independent optical excitation of distinct neural populations. Nat Methods 11:338–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleinlogel S, Feldbauer K, Dempski RE, Fotis H, Wood PG, Bamann C, Bamberg E (2011) Ultra light-sensitive and fast neuronal activation with the Ca(2)+-permeable channelrhodopsin CatCh. Nat Neurosci 14:513–518

    Article  CAS  PubMed  Google Scholar 

  • Kolbe M, Besir H, Essen LO, Oesterhelt D (2000) Structure of the light-driven chloride pump halorhodopsin at 1.8 A resolution. Science 288:1390–1396

    Article  CAS  PubMed  Google Scholar 

  • Kovalev K, Astashkin R, Gushchin I, Orekhov P, Volkov D, Zinovev E, Marin E, Rulev M, Alekseev A, Royant A et al (2020) Molecular mechanism of light-driven sodium pumping. Nat Commun 11:2137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krause N, Engelhard C, Heberle J, Schlesinger R, Bittl R (2013) Structural differences between the closed and open states of channelrhodopsin-2 as observed by EPR spectroscopy. FEBS Lett 587:3309–3313

    Article  CAS  PubMed  Google Scholar 

  • Kuhne J, Eisenhauer K, Ritter E, Hegemann P, Gerwert K, Bartl F (2015) Early formation of the ion-conducting pore in channelrhodopsin-2. Angew Chem Int Ed Engl 54:4953–4957

    Article  CAS  PubMed  Google Scholar 

  • Li X, Gutierrez DV, Hanson MG, Han J, Mark MD, Chiel H, Hegemann P, Landmesser LT, Herlitze S (2005) Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc Natl Acad Sci U S A 102:17816–17821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Govorunova EG, Sineshchekov OA, Spudich JL (2014) Role of a helix B lysine residue in the photoactive site in channelrhodopsins. Biophys J 106:1607–1617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin JY, Lin MZ, Steinbach P, Tsien RY (2009) Characterization of engineered channelrhodopsin variants with improved properties and kinetics. Biophys J 96:1803–1814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin JY, Knutsen PM, Muller A, Kleinfeld D, Tsien RY (2013) ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat Neurosci 16:1499–1508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lorenz-Fonfria VA, Resler T, Krause N, Nack M, Gossing M, Fischer von Mollard G, Bamann C, Bamberg E, Schlesinger R, Heberle J (2013) Transient protonation changes in channelrhodopsin-2 and their relevance to channel gating. Proc Natl Acad Sci U S A 110:E1273–E1281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luck M, Mathes T, Bruun S, Fudim R, Hagedorn R, Tran Nguyen TM, Kateriya S, Kennis JT, Hildebrandt P, Hegemann P (2012) A photochromic histidine kinase rhodopsin (HKR1) that is bimodally switched by ultraviolet and blue light. J Biol Chem 287:40083–40090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mager T, Lopez de la Morena D, Senn V, Schlotte J, D Errico A, Feldbauer K, Wrobel C, Jung S, Bodensiek K, Rankovic V et al (2018) High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics. Nat Commun 9:1750

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mahn M, Prigge M, Ron S, Levy R, Yizhar O (2016) Biophysical constraints of optogenetic inhibition at presynaptic terminals. Nat Neurosci 19:554–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marshel JH, Kim YS, Machado TA, Quirin S, Benson B, Kadmon J, Raja C, Chibukhchyan A, Ramakrishnan C, Inoue M et al (2019) Cortical layer-specific critical dynamics triggering perception. Science 365:eaaw5202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuno-Yagi A, Mukohata Y (1977) Two possible roles of bacteriorhodopsin; a comparative study of strains of Halobacterium halobium differing in pigmentation. Biochem Biophys Res Commun 78:237–243

    Article  CAS  PubMed  Google Scholar 

  • Muller M, Bamann C, Bamberg E, Kuhlbrandt W (2011) Projection structure of channelrhodopsin-2 at 6 A resolution by electron crystallography. J Mol Biol 414:86–95

    Article  PubMed  CAS  Google Scholar 

  • Muller M, Bamann C, Bamberg E, Kuhlbrandt W (2015) Light-induced helix movements in channelrhodopsin-2. J Mol Biol 427:341–349

    Article  PubMed  CAS  Google Scholar 

  • Nagel G, Ollig D, Fuhrmann M, Kateriya S, Musti AM, Bamberg E, Hegemann P (2002) Channelrhodopsin-1: a light-gated proton channel in green algae. Science 296:2395–2398

    Article  CAS  PubMed  Google Scholar 

  • Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P, Ollig D, Hegemann P, Bamberg E (2003) Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A 100:13940–13945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagel G, Brauner M, Liewald JF, Adeishvili N, Bamberg E, Gottschalk A (2005) Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses. Curr Biol 15:2279–2284

    Article  CAS  PubMed  Google Scholar 

  • Nango E, Royant A, Kubo M, Nakane T, Wickstrand C, Kimura T, Tanaka T, Tono K, Song C, Tanaka R et al (2016) A three-dimensional movie of structural changes in bacteriorhodopsin. Science 354:1552–1557

    Article  CAS  PubMed  Google Scholar 

  • Nogly P, Weinert T, James D, Carbajo S, Ozerov D, Furrer A, Gashi D, Borin V, Skopintsev P, Jaeger K et al (2018) Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser. Science:361

    Google Scholar 

  • Oda K, Vierock J, Oishi S, Rodriguez-Rozada S, Taniguchi R, Yamashita K, Wiegert JS, Nishizawa T, Hegemann P, Nureki O (2018) Crystal structure of the red light-activated channelrhodopsin Chrimson. Nat Commun 9:3949

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oesterhelt D, Stoeckenius W (1971) Rhodopsin-like protein from the purple membrane of Halobacterium halobium. Nat New Biol 233:149–152

    Article  CAS  PubMed  Google Scholar 

  • Oppermann J, Fischer P, Silapetere A, Liepe B, Rodriguez-Rozada S, Flores-Uribe J, Peter E, Keidel A, Vierock J, Kaufmann J et al (2019) MerMAIDs: a family of metagenomically discovered marine anion-conducting and intensely desensitizing channelrhodopsins. Nat Commun 10:3315

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pebay-Peyroula E, Rummel G, Rosenbusch JP, Landau EM (1997) X-ray structure of bacteriorhodopsin at 2.5 angstroms from microcrystals grown in lipidic cubic phases. Science 277:1676–1681

    Article  CAS  PubMed  Google Scholar 

  • Prigge M, Schneider F, Tsunoda SP, Shilyansky C, Wietek J, Deisseroth K, Hegemann P (2012) Color-tuned channelrhodopsins for multiwavelength optogenetics. J Biol Chem 287:31804–31812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Radu I, Bamann C, Nack M, Nagel G, Bamberg E, Heberle J (2009) Conformational changes of channelrhodopsin-2. J Am Chem Soc 131:7313–7319

    Article  CAS  PubMed  Google Scholar 

  • Rajasethupathy P, Sankaran S, Marshel JH, Kim CK, Ferenczi E, Lee SY, Berndt A, Ramakrishnan C, Jaffe A, Lo M et al (2015) Projections from neocortex mediate top-down control of memory retrieval. Nature 526:653–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richards R, Dempski RE (2012) Re-introduction of transmembrane serine residues reduce the minimum pore diameter of channelrhodopsin-2. PLoS One 7:e50018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ritter E, Stehfest K, Berndt A, Hegemann P, Bartl FJ (2008) Monitoring light-induced structural changes of Channelrhodopsin-2 by UV-visible and Fourier transform infrared spectroscopy. J Biol Chem 283:35033–35041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rost BR, Schneider-Warme F, Schmitz D, Hegemann P (2017) Optogenetic tools for subcellular applications in neuroscience. Neuron 96:572–603

    Article  CAS  PubMed  Google Scholar 

  • Sattig T, Rickert C, Bamberg E, Steinhoff HJ, Bamann C (2013) Light-induced movement of the transmembrane helix B in channelrhodopsin-2. Angew Chem Int Ed Engl 52:9705–9708

    Article  CAS  PubMed  Google Scholar 

  • Scheib U, Stehfest K, Gee CE, Korschen HG, Fudim R, Oertner TG, Hegemann P (2015) The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling. Sci Sign 8:rs8

    Google Scholar 

  • Scholz N, Guan C, Nieberler M, Grotemeyer A, Maiellaro I, Gao S, Beck S, Pawlak M, Sauer M, Asan E et al (2017) Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons. elife 6:28360

    Article  Google Scholar 

  • Sineshchekov OA, Litvin FF, Keszthelyi L (1990) Two components of photoreceptor potential in phototaxis of the flagellated green alga Haematococcus pluvialis. Biophys J 57:33–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sineshchekov OA, Jung KH, Spudich JL (2002) Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii. Proc Natl Acad Sci U S A 99:8689–8694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sineshchekov OA, Govorunova EG, Li H, Spudich JL (2015) Gating mechanisms of a natural anion channelrhodopsin. Proc Natl Acad Sci U S A 112:14236–14241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sineshchekov OA, Govorunova EG, Li H, Wang Y, Melkonian M, Wong GK, Brown LS, Spudich JL (2020) Conductance mechanisms of rapidly desensitizing cation Channelrhodopsins from Cryptophyte algae. mBio 11:e00657–20

    Google Scholar 

  • Skopintsev P, Ehrenberg D, Weinert T, James D, Kar RK, Johnson PJM, Ozerov D, Furrer A, Martiel I, Dworkowski F et al (2020) Femtosecond-to-millisecond structural changes in a light-driven sodium pump. Nature. Epub ahead of print

    Google Scholar 

  • Sugiyama Y, Wang H, Hikima T, Sato M, Kuroda J, Takahashi T, Ishizuka T, Yawo H (2009) Photocurrent attenuation by a single polar-to-nonpolar point mutation of channelrhodopsin-2. Photochem Photobiol Sci 8:328–336

    Article  CAS  PubMed  Google Scholar 

  • Suzuki T, Yamasaki K, Fujita S, Oda K, Iseki M, Yoshida K, Watanabe M, Daiyasu H, Toh H, Asamizu E et al (2003) Archaeal-type rhodopsins in Chlamydomonas: model structure and intracellular localization. Biochem Biophys Res Commun 301:711–717

    Article  CAS  PubMed  Google Scholar 

  • Szundi I, Bogomolni R, Kliger DS (2015) Platymonas subcordiformis Channelrhodopsin-2 (PsChR2) function: II. Relationship of the photochemical reaction cycle to channel currents. J Biol Chem 290:16585–16594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takemoto M, Kato HE, Koyama M, Ito J, Kamiya M, Hayashi S, Maturana AD, Deisseroth K, Ishitani R, Nureki O (2015) Molecular dynamics of Channelrhodopsin at the early stages of channel opening. PLoS One 10:e0131094

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vierock J, Grimm C, Nitzan N, Hegemann P (2017) Molecular determinants of proton selectivity and gating in the red-light activated channelrhodopsin Chrimson. Sci Rep 7:9928

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vogt A, Silapetere A, Grimm C, Heiser F, Ancina Moller M, Hegemann P (2019) Engineered passive potassium conductance in the KR2 sodium pump. Biophys J 116:1941–1951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volkov O, Kovalev K, Polovinkin V, Borshchevskiy V, Bamann C, Astashkin R, Marin E, Popov A, Balandin T, Willbold D et al (2017) Structural insights into ion conduction by channelrhodopsin 2. Science 358:eaan8862

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Sugiyama Y, Hikima T, Sugano E, Tomita H, Takahashi T, Ishizuka T, Yawo H (2009) Molecular determinants differentiating photocurrent properties of two channelrhodopsins from chlamydomonas. J Biol Chem 284:5685–5696

    Article  CAS  PubMed  Google Scholar 

  • Watanabe HC, Welke K, Sindhikara DJ, Hegemann P, Elstner M (2013) Towards an understanding of channelrhodopsin function: simulations lead to novel insights of the channel mechanism. J Mol Biol 425:1795–1814

    Article  CAS  PubMed  Google Scholar 

  • Weinert T, Skopintsev P, James D, Dworkowski F, Panepucci E, Kekilli D, Furrer A, Brunle S, Mous S, Ozerov D et al (2019) Proton uptake mechanism in bacteriorhodopsin captured by serial synchrotron crystallography. Science 365:61–65

    Article  CAS  PubMed  Google Scholar 

  • Wickstrand C, Dods R, Royant A, Neutze R (2015) Bacteriorhodopsin: would the real structural intermediates please stand up? Biochim Biophys Acta 1850:536–553

    Article  CAS  PubMed  Google Scholar 

  • Wiegert JS, Mahn M, Prigge M, Printz Y, Yizhar O (2017) Silencing neurons: tools, applications, and experimental constraints. Neuron 95:504–529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wietek J, Wiegert JS, Adeishvili N, Schneider F, Watanabe H, Tsunoda SP, Vogt A, Elstner M, Oertner TG, Hegemann P (2014) Conversion of channelrhodopsin into a light-gated chloride channel. Science 344:409–412

    Article  CAS  PubMed  Google Scholar 

  • Wietek J, Beltramo R, Scanziani M, Hegemann P, Oertner TG, Wiegert JS (2015) An improved chloride-conducting channelrhodopsin for light-induced inhibition of neuronal activity in vivo. Sci Rep 5:14807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wietek J, Rodriguez-Rozada S, Tutas J, Tenedini F, Grimm C, Oertner TG, Soba P, Hegemann P, Wiegert JS (2017) Anion-conducting channelrhodopsins with tuned spectra and modified kinetics engineered for optogenetic manipulation of behavior. Sci Rep 7:14957

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamauchi Y, Konno M, Ito S, Tsunoda SP, Inoue K, Kandori H (2017) Molecular properties of a DTD channelrhodopsin from Guillardia theta. Biophys Physicobiol 14:57–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT et al (2011) Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshida K, Tsunoda SP, Brown LS, Kandori H (2017) A unique choanoflagellate enzyme rhodopsin exhibits light-dependent cyclic nucleotide phosphodiesterase activity. J Biol Chem 292:7531–7541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zabelskii D, Alekseev A, Kovalev K, Oliviera AS, Balandin T, Soloviov D, Bratanov D, Volkov L, Vaganova S, Astashkin R et al (2020) Viral channelrhodopsins: calcium-dependent Na+/K+ selective light-gated channels. bioRxiv. https://doi.org/10.1101/2020.02.14.949966

  • Zhang F, Wang LP, Brauner M, Liewald JF, Kay K, Watzke N, Wood PG, Bamberg E, Nagel G, Gottschalk A et al (2007) Multimodal fast optical interrogation of neural circuitry. Nature 446:633–639

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Prigge M, Beyriere F, Tsunoda SP, Mattis J, Yizhar O, Hegemann P, Deisseroth K (2008) Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri. Nat Neurosci 11:631–633

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgments

This work was supported by JST PRESTO (JPMJPR1782), UTEC-Utokyo FSI Research Grant Program, Yamada Science Foundation, and The Nakajima Foundation.

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Correspondence to Hideaki E. Kato .

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Kato, H.E. (2021). Structure–Function Relationship of Channelrhodopsins. In: Yawo, H., Kandori, H., Koizumi, A., Kageyama, R. (eds) Optogenetics. Advances in Experimental Medicine and Biology, vol 1293. Springer, Singapore. https://doi.org/10.1007/978-981-15-8763-4_3

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