Abstract
Photoreceptors are found in all kingdoms of life and mediate crucial responses to environmental challenges. Nature has evolved various types of photoresponsive protein structures with different chromophores and signaling concepts for their given purpose. The abundance of these signaling proteins as found nowadays by (meta-)genomic screens enriched the palette of optogenetic tools significantly. In addition, molecular insights into signal transduction mechanisms and design principles from biophysical studies and from structural and mechanistic comparison of homologous proteins opened seemingly unlimited possibilities for customizing the naturally occurring proteins for a given optogenetic task. Here, a brief overview on the photoreceptor concepts already established as optogenetic tools in natural or engineered form, their photochemistry and their signaling/design principles is given. Finally, so far not regarded photosensitive modules and protein architectures with potential for optogenetic application are described.
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References
Hauser FE, van Hazel I, Chang BSW (2014) Spectral tuning in vertebrate short wavelength-sensitive 1 (SWS1) visual pigments: can wavelength sensitivity be inferred from sequence data? J Exp Zool B 322(7):529–539
Thoen HH, How MJ, Chiou TH, Marshall J (2014) A different form of color vision in mantis shrimp. Science 343(6169):411–413
Rockwell NC, Duanmu D, Martin SS, Bachy C, Price DC, Bhattacharya D et al (2014) Eukaryotic algal phytochromes span the visible spectrum. Proc Natl Acad Sci U S A 111(10):3871–3876
Ishizuka T, Shimada T, Okajima K, Yoshihara S, Ochiai Y, Katayama M et al (2006) Characterization of cyanobacteriochrome TePixJ from a thermophilic cyanobacterium Thermosynechococcus elongatus strain BP-1. Plant Cell Physiol 47(9):1251–1261
Losi A, Gärtner W (2012) The evolution of flavin-binding photoreceptors: an ancient chromophore serving trendy blue-light sensors. Annu Rev Plant Biol 63:49–72
Bouly JP, Schleicher E, Dionisio-Sese M, Vandenbussche F, Van Der Straeten D, Bakrim N et al (2007) Cryptochrome blue light photoreceptors are activated through interconversion of flavin redox states. J Biol Chem 282(13):9383–9391
Carell T, Burgdorf LT, Kundu LM, Cichon M (2001) The mechanism of action of DNA photolyases. Curr Opin Chem Biol 5(5):491–498
Beel B, Prager K, Spexard M, Sasso S, Weiss D, Muller N et al (2012) A flavin binding cryptochrome photoreceptor responds to both blue and red light in Chlamydomonas reinhardtii. Plant Cell 24(7):2992–3008
Jenkins GI (2014) The UV-B photoreceptor UVR8: from structure to physiology. Plant Cell 26(1):21–37
Meyer TE, Kyndt JA, Memmi S, Moser T, Colon-Acevedo B, Devreese B et al (2012) The growing family of photoactive yellow proteins and their presumed functional roles. Photochem Photobiol Sci 11(10):1495–1514
Ortiz-Guerrero JM, Polanco MC, Murillo FJ, Padmanabhan S, Elias-Arnanz M (2011) Light-dependent gene regulation by a coenzyme B12-based photoreceptor. Proc Natl Acad Sci U S A 108(18):7565–7570
Mathes T, van Stokkum IHM, Kennis JTM (2014) Photoactivation mechanisms of flavin-binding photoreceptors revealed through ultrafast spectroscopy and global analysis methods. Flavins Flavoproteins Methods Protocols 1146:401–442
Kennis JTM, Mathes T (2013) Molecular eyes: proteins that transform light into biological information. Interface Focus 3(5):20130005
Barlow RB, Birge RR, Kaplan E, Tallent JR (1993) On the molecular-origin of photoreceptor noise. Nature 366(6450):64–66
Stujenske JM, Spellman T, Gordon JA (2015) Modeling the spatiotemporal dynamics of light and heat propagation for in vivo optogenetics. Cell Rep 12(3):525–534
Mathes T, Heilmann M, Pandit A, Zhu J, Ravensbergen J, Kloz M et al (2015) Proton-coupled electron transfer constitutes the photoactivation mechanism of the plant photoreceptor UVR8. J Am Chem Soc 137(25):8113–8120
Heilmann M, Christie JM, Kennis JT, Jenkins GI, Mathes T (2015) Photoinduced transformation of UVR8 monitored by vibrational and fluorescence spectroscopy. Photochem Photobiol Sci 14(2):252–257
Ziegler T, Möglich A (2015) Photoreceptor engineering. Front Mol Biosci 2:30
Klapoetke NC, Murata Y, Kim SS, Pulver SR, Birdsey-Benson A, Cho YK et al (2014) Independent optical excitation of distinct neural populations. Nat Methods 11(3):338–346
Pathak GP, Losi A, Gärtner W (2011) Metagenome-based screening reveals worldwide distribution of LOV-domain proteins. Photochem Photobiol 88(1):107–118
Pathak GP, Ehrenreich A, Losi A, Streit WR, Gärtner W (2009) Novel blue light-sensitive proteins from a metagenomic approach. Environ Microbiol 11(9):2388–2399
Prigge M, Schneider F, Tsunoda SP, Shilyansky C, Wietek J, Deisseroth K et al (2012) Color-tuned channelrhodopsins for multiwavelength optogenetics. J Biol Chem 287(38):31804–31812
Wietek J, Wiegert JS, Adeishvili N, Schneider F, Watanabe H, Tsunoda SP et al (2014) Conversion of channelrhodopsin into a light-gated chloride channel. Science 344(6182):409–412
Kleinlogel S, Feldbauer K, Dempski RE, Fotis H, Wood PG, Bamann C et al (2011) Ultra light-sensitive and fast neuronal activation with the Ca(2)+-permeable channelrhodopsin CatCh. Nat Neurosci 14(4):513–518
Berndt A, Yizhar O, Gunaydin LA, Hegemann P, Deisseroth K (2009) Bi-stable neural state switches. Nat Neurosci 12(2):229–234
Weissenberger S, Schultheis C, Liewald JF, Erbguth K, Nagel G, Gottschalk A (2011) PACalpha--an optogenetic tool for in vivo manipulation of cellular cAMP levels, neurotransmitter release, and behavior in Caenorhabditis elegans. J Neurochem 116(4):616–625
Stierl M, Stumpf P, Udwari D, Gueta R, Hagedorn R, Losi A et al (2011) Light modulation of cellular cAMP by a small bacterial photoactivated adenylyl cyclase, bPAC, of the soil bacterium Beggiatoa. J Biol Chem 286(2):1181–1188
Schröder-Lang S, Schwarzel M, Seifert R, Strunker T, Kateriya S, Looser J et al (2007) Fast manipulation of cellular cAMP level by light in vivo. Nat Methods 4(1):39–42
Chen ZH, Raffelberg S, Losi A, Schaap P, Gärtner W (2014) A cyanobacterial light activated adenylyl cyclase partially restores development of a Dictyostelium discoideum, adenylyl cyclase a null mutant. J Biotechnol 191:246–249
Möglich A, Moffat K (2010) Engineered photoreceptors as novel optogenetic tools. Photochem Photobiol Sci 9(10):1286–1300
Takahashi F, Yamagata D, Ishikawa M, Fukamatsu Y, Ogura Y, Kasahara M et al (2007) AUREOCHROME, a photoreceptor required for photomorphogenesis in stramenopiles. Proc Natl Acad Sci U S A 104(49):19625–19630
Hisatomi O, Nakatani Y, Takeuchi K, Takahashi F, Kataoka H (2014) Blue light-induced dimerization of monomeric aureochrome-1 enhances its affinity for the target sequence. J Biol Chem 289(25):17379–17391
Wang X, Chen XJ, Yang Y (2012) Spatiotemporal control of gene expression by a light-switchable transgene system. Nat Methods 9(3):266–269
Motta-Mena LB, Reade A, Mallory MJ, Glantz S, Weiner OD, Lynch KW et al (2014) An optogenetic gene expression system with rapid activation and deactivation kinetics. Nat Chem Biol 10(3):196–202
Harper SM, Neil LC, Gardner KH (2003) Structural basis of a phototropin light switch. Science 301(5639):1541–1544
Wu YI, Frey D, Lungu OI, Jaehrig A, Schlichting I, Kuhlman B et al (2009) A genetically encoded photoactivatable Rac controls the motility of living cells. Nature 461(7260):104–108
Schmidt D, Tillberg PW, Chen F, Boyden ES (2014) A fully genetically encoded protein architecture for optical control of peptide ligand concentration. Nat Commun 5:3019
Cosentino C, Alberio L, Gazzarrini S, Aquila M, Romano E, Cermenati S et al (2015) Optogenetics. Engineering of a light-gated potassium channel. Science 348(6235):707–710
Morgan SA, Al-Abdul-Wahid S, Woolley GA (2010) Structure-based design of a photocontrolled DNA binding protein. J Mol Biol 399(1):94–112
Strickland D, Lin Y, Wagner E, Hope CM, Zayner J, Antoniou C et al (2012) TULIPs: tunable, light-controlled interacting protein tags for cell biology. Nat Methods 9(4):379–384
Pathak GP, Strickland D, Vrana JD, Tucker CL (2014) Benchmarking of optical dimerizer systems. ACS Synth Biol 3(11):832–838
Reis JM, Burns DC, Woolley GA (2014) Optical control of protein-protein interactions via blue light-induced domain swapping. Biochemistry 53(30):5008–5016
Kennedy MJ, Hughes RM, Peteya LA, Schwartz JW, Ehlers MD, Tucker CL (2010) Rapid blue-light-mediated induction of protein interactions in living cells. Nat Methods 7(12):973–975, advance online publication
Toettcher JE, Gong D, Lim WA, Weiner OD (2011) Light-based feedback for controlling intracellular signaling dynamics. Nat Methods 8(10):837–839
Bugaj LJ, Choksi AT, Mesuda CK, Kane RS, Schaffer DV (2013) Optogenetic protein clustering and signaling activation in mammalian cells. Nat Methods 10(3):249–252
Taslimi A, Vrana JD, Chen D, Borinskaya S, Mayer BJ, Kennedy MJ et al (2014) An optimized optogenetic clustering tool for probing protein interaction and function. Nat Commun 5:4925
Che DL, Duan L, Zhang K, Cui B (2015) The dual characteristics of light-induced cryptochrome 2, homo-oligomerization and heterodimerization, for optogenetic manipulation in mammalian cells. ACS Synth Biol 4(10):1124–1135
Kianianmomeni A (2015) UVB-based optogenetic tools. Trends Biotechnol 33(2):59–61
Möglich A, Ayers RA, Moffat K (2009) Design and signaling mechanism of light-regulated histidine kinases. J Mol Biol 385(5):1433–1444
Gasser C, Taiber S, Yeh C-M, Wittig CH, Hegemann P, Ryu S et al (2014) Engineering of a red-light-activated human cAMP/cGMP-specific phosphodiesterase. Proc Natl Acad Sci U S A 111(24):8803–8808
Ryu M-H, Kang I-H, Nelson MD, Jensen TM, Lyuksyutova AI, Siltberg-Liberles J et al (2014) Engineering adenylate cyclases regulated by near-infrared window light. Proc Natl Acad Sci U S A 111(28):10167–10172
Han Y, Braatsch S, Osterloh L, Klug G (2004) A eukaryotic BLUF domain mediates light-dependent gene expression in the purple bacterium Rhodobacter sphaeroides 2.4.1. Proc Natl Acad Sci U S A 101(33):12306–12311
Strickland D, Moffat K, Sosnick TR (2008) Light-activated DNA binding in a designed allosteric protein. Proc Natl Acad Sci 105(31):10709–10714
Ohlendorf R, Vidavski RR, Eldar A, Moffat K, Möglich A (2012) From dusk till dawn: one-plasmid systems for light-regulated gene expression. J Mol Biol 416(4):534–542
Qi Y, Rao F, Luo Z, Liang Z-X (2009) A flavin cofactor-binding PAS domain regulates c-di-GMP synthesis in AxDGC2 from Acetobacter xylinum. Biochemistry 48(43):10275–10285
Barends TR, Hartmann E, Griese JJ, Beitlich T, Kirienko NV, Ryjenkov DA et al (2009) Structure and mechanism of a bacterial light-regulated cyclic nucleotide phosphodiesterase. Nature 459(7249):1015–1018
Kanazawa T, Ren S, Maekawa M, Hasegawa K, Arisaka F, Hyodo M et al (2010) Biochemical and physiological characterization of a BLUF protein−EAL protein complex involved in blue light-dependent degradation of cyclic diguanylate in the purple bacterium Rhodopseudomonas palustris. Biochemistry 49(50):10647–10655
Schaap P (2013) Cyclic di-nucleotide signaling enters the eukaryote domain. IUBMB Life 65(11):897–903
Broichhagen J, Frank JA, Trauner D (2015) A roadmap to success in photopharmacology. Acc Chem Res 48(7):1947–1960
Fehrentz T, Schonberger M, Trauner D (2011) Optochemical genetics. Angew Chem Int Ed Engl 50(51):12156–12182
Luck M, Mathes T, Bruun S, Fudim R, Hagedorn R, Nguyen TMT et al (2012) A photochromic histidine kinase rhodopsin (HKR1) that is bimodally switched by ultraviolet and blue light. J Biol Chem 287(47):40083–40090
Sexton TJ, Golczak M, Palczewski K, Van Gelder RN (2012) Melanopsin is highly resistant to light and chemical bleaching in vivo. J Biol Chem 287(25):20888–20897
van Wyk M, Pielecka-Fortuna J, Lowel S, Kleinlogel S (2015) Restoring the ON switch in blind retinas: opto-mGluR6, a next-generation, cell-tailored optogenetic tool. PLoS Biol 13(5):e1002143
Beiert T, Bruegmann T, Sasse P (2014) Optogenetic activation of Gq signalling modulates pacemaker activity of cardiomyocytes. Cardiovasc Res 102(3):507–516
Avelar GM, Schumacher RI, Zaini PA, Leonard G, Richards TA, Gomes SL (2014) A rhodopsin-guanylyl cyclase gene fusion functions in visual perception in a fungus. Curr Biol 24(11):1234–1240
Scheib U, Stehfest K, Gee CE, Korschen HG, Fudim R, Oertner TG et al (2015) The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling. Sci Signal 8(389):rs8
Gao S, Nagpal J, Schneider MW, Kozjak-Pavlovic V, Nagel G, Gottschalk A (2015) Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp. Nat Commun 6:8046
Ryu MH, Moskvin OV, Siltberg-Liberles J, Gomelsky M (2010) Natural and engineered photoactivated nucleotidyl cyclases for optogenetic applications. J Biol Chem 285(53):41501–41508
Balashov SP, Imasheva ES, Boichenko VA, Anton J, Wang JM, Lanyi JK (2005) Xanthorhodopsin: a proton pump with a light-harvesting carotenoid antenna. Science 309(5743):2061–2064
Wilson A, Punginelli C, Gall A, Bonetti C, Alexandre M, Routaboul J-M et al (2008) A photoactive carotenoid protein acting as light intensity sensor. Proc Natl Acad Sci U S A 105(33):12075–12080
Leverenz RL, Sutter M, Wilson A, Gupta S, Thurotte A, de Carbon CB et al (2015) A 12 angstrom carotenoid translocation in a photoswitch associated with cyanobacterial photoprotection. Science 348(6242):1463–1466
Gwizdala M, Wilson A, Kirilovsky D (2011) In vitro reconstitution of the cyanobacterial photoprotective mechanism mediated by the orange carotenoid protein in synechocystis PCC 6803. Plant Cell 23(7):2631–2643
Auldridge ME, Satyshur KA, Anstrom DM, Forest KT (2012) Structure-guided engineering enhances a phytochrome-based infrared fluorescent protein. J Biol Chem 287(10):7000–7009
Takala H, Bjorling A, Linna M, Westenhoff S, Ihalainen JA (2015) Light-induced changes in the dimerization interface of bacteriophytochromes. J Biol Chem 290(26):16383–16392
Zemelman BV, Lee GA, Ng M, Miesenböck G (2002) Selective photostimulation of genetically chARGed neurons. Neuron 33(1):15–22
Airan RD, Thompson KR, Fenno LE, Bernstein H, Deisseroth K (2009) Temporally precise in vivo control of intracellular signalling. Nature 458(7241):1025–1029
Kim JM, Hwa J, Garriga P, Reeves PJ, RajBhandary UL, Khorana HG (2005) Light-driven activation of beta 2-adrenergic receptor signaling by a chimeric rhodopsin containing the beta 2-adrenergic receptor cytoplasmic loops. Biochemistry 44(7):2284–2292
Oh E, Maejima T, Liu C, Deneris E, Herlitze S (2010) Substitution of 5-HT1A receptor signaling by a light-activated G protein-coupled receptor. J Biol Chem 285(40):30825–30836
Xiang Y, Yuan Q, Vogt N, Looger LL, Jan LY, Jan YN (2010) Light-avoidance-mediating photoreceptors tile the Drosophila larval body wall. Nature 468(7326):921–926
Liu J, Ward A, Gao J, Dong Y, Nishio N, Inada H et al (2010) C. elegans phototransduction requires a G protein-dependent cGMP pathway and a taste receptor homolog. Nat Neurosci 13(6):715–722
Ward A, Liu J, Feng Z, Xu XZ (2008) Light-sensitive neurons and channels mediate phototaxis in C. elegans. Nat Neurosci 11(8):916–922
Edwards SL, Charlie NK, Milfort MC, Brown BS, Gravlin CN, Knecht JE et al (2008) A novel molecular solution for ultraviolet light detection in Caenorhabditis elegans. PLoS Biol 6(8):e198
Bhatla N, Horvitz HR (2015) Light and hydrogen peroxide inhibit C. elegans Feeding through gustatory receptor orthologs and pharyngeal neurons. Neuron 85(4):804–818
Jost M, Fernández-Zapata J, Polanco MC, Ortiz-Guerrero JM, Chen PY-T, Kang G, Padmanabhan S, ElÃas-Arnanz M & Drennan CL (2015) Structural basis for gene regulation by a B12-dependent photoreceptor. Nature 526, 536–541
Muller F, Walker WH, Massey V, Brustlei M, Hemmeric P (1972) Light-absorption studies on neutral flavin radicals. Eur J Biochem 25(3):573–580
Gauden M, Yeremenko S, Laan W, van Stokkum IHM, Ihalainen JA, van Grondelle R et al (2005) Photocycle of the flavin-binding photoreceptor AppA, a bacterial transcriptional antirepressor of photosynthesis genes. Biochemistry 44(10):3653–3662
Zirak P, Penzkofer A, Lehmpfuhl C, Mathes T, Hegemann P (2007) Absorption and emission spectroscopic characterization of blue-light receptor Slr1694 from Synechocystis sp. PCC6803. J Photochem Photobiol B 86(1):22–34
Zirak P, Penzkofer A, Schiereis T, Hegemann P, Jung A, Schlichting I (2006) Photodynamics of the small BLUF protein BlrB from Rhodobacter sphaeroides. J Photochem Photobiol B 83(3):180–194
Kottke T, Heberle J, Hehn D, Dick B, Hegemann P (2003) Phot-LOV1: photocycle of a blue-light receptor domain from the green alga Chlamydomonas reinhardtii. Biophys J 84(2 Pt 1):1192–1201
Kennis JTM, Crosson S, Gauden M, van Stokkum IH, Moffat K, van Grondelle R (2003) Primary reactions of the LOV2 domain of phototropin, a plant blue-light photoreceptor. Biochemistry 42(12):3385–3392
Müller P, Bouly JP, Hitomi K, Balland V, Getzoff ED, Ritz T et al (2014) ATP binding turns plant cryptochrome into an efficient natural photoswitch. Sci Rep 4
Giovani B, Byrdin M, Ahmad M, Brettel K (2003) Light-induced electron transfer in a cryptochrome blue-light photoreceptor. Nat Struct Mol Biol 10(6):489–490
Losi A, Gensch T, van der Horst MA, Hellingwerf KJ, Braslavsky SE (2005) Hydrogen-bond network probed by time-resolved optoacoustic spectroscopy: photoactive yellow protein and the effect of E46Q and E46A mutations. Phys Chem Chem Phys 7(10):2229–2236
Lincoln CN, Fitzpatrick AE, van Thor JJ (2012) Photoisomerisation quantum yield and non-linear cross-sections with femtosecond excitation of the photoactive yellow protein. Phys Chem Chem Phys 14(45):15752–15764
Fan HY, Morgan SA, Brechun KE, Chen YY, Jaikaran ASI, Woolley GA (2011) Improving a designed photocontrolled DNA-binding protein. Biochemistry 50(7):1226–1237
Lamparter T, Esteban B, Hughes J (2001) Phytochrome Cph1 from the cyanobacterium Synechocystis PCC6803—purification, assembly, and quaternary structure. Eur J Biochem 268(17):4720–4730
Vierstra RD, Quail PH (1983) Photochemistry of 124 kilodalton Avena phytochrome in vitro. Plant Physiol 72(1):264–267
Pennacchietti F, Losi A, Xu XL, Zhao KH, Gärtner W, Viappiani C et al (2015) Photochromic conversion in a red/green cyanobacteriochrome from Synechocystis PCC6803: quantum yields in solution and photoswitching dynamics in living E. coli cells. Photochem Photobiol Sci 14(2):229–237
Popot JL, Gerchman SE, Engelman DM (1987) Refolding of bacteriorhodopsin in lipid bilayers—a thermodynamically controlled 2-stage process. J Mol Biol 198(4):655–676
Govindjee R, Balashov SP, Ebrey TG (1990) Quantum efficiency of the photochemical cycle of bacteriorhodopsin. Biophys J 58(3):597–608
Pace CN, Vajdos F, Fee L, Grimsley G, Gray T (1995) How to measure and predict the molar absorption-coefficient of a protein. Protein Sci 4(11):2411–2423
Chen D, Gibson ES, Kennedy MJ (2013) A light-triggered protein secretion system. J Cell Biol 201(4):631–640
Müller K, Engesser R, Schulz S, Steinberg T, Tomakidi P, Weber CC et al (2013) Multi-chromatic control of mammalian gene expression and signaling. Nucleic Acids Res 41(12):e124
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I would like to thank John Kennis and Peter Hegemann for generous support over the last years.
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Mathes, T. (2016). Natural Resources for Optogenetic Tools. In: Kianianmomeni, A. (eds) Optogenetics. Methods in Molecular Biology, vol 1408. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3512-3_2
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