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Project B2

Gating and ion transport dynamics in channelrhodopsins and light-driven pumps

Principal Investigator: Prof. Dr. Peter Hegemann (HU)

During the recent funding period, we characteri­zed anion-conducting channelrhodopsins (ACRs) including the novel family of MerMAIDs identified by Tara Ocean metagenomics. Within the next funding period, we will further study MerMAIDs and continue with the recently identified viral ACRs and their relatives of their algal prasinophyte hosts. The second new class of interest will be cryptophyte cation-conducting channelrhodopsins (CCRs) that show large photocurrents and relation to light-driven pumps. Our studies will provide a concise concept for light-activated uni- and bi-directional ion conductance.



Fischer, P., Schiewer, E., Broser, M., Busse, W., Spreen, A., Grosse, M., Hegemann, P. and Bartl, F. (2024). The Functionality of the DC Pair in a Rhodopsin Guanylyl Cyclase from Catenaria anguillulaeJ Mol Biol, 436, 5: 168375. doi: 10.1016/j.jmb.2023.168375.

Fernandez Lahore, R.G., Pampaloni, N.P., Schiewer, E., Heim, M.M., Tillert, L., Vierock, J., Oppermann, J., Walther, J., Schmitz, D., Owald, D., Plested, A.J.R., Rost, B.R. and Hegemann, P. (2022). Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling. Nat Commun, 13, 1: 7844. doi: 10.1038/s41467-022-35373-4.

Baidukova, O., Oppermann, J., Kelterborn, S., Fernandez Lahore, R.G., Schumacher, D., Evers, H., Kamrani, Y.Y. and Hegemann, P. (2022). Gating and ion selectivity of Channelrhodopsins are critical for photo-activated orientation of Chlamydomonas as shown by in vivo point mutation. Nature Commun, 13, 1: 7253. doi: 10.1038/s41467-022-35018-6.

Broser, M., Andruniow, T., Kraskov, A., Palombo, R., Katz, S., Kloz, M., Dostál, J., Bernardo, C., Kennis, J., Hegemann, P., Olivucci M., and Hildebrandt, P. (2023). Experimental assessment of the electronic and geometrical structure of a near-infrared absorbing and highly fluorescent microbial rhodopsin. J Phys Chem Lett. doi: 10.1021/acs.jpclett.3c02167.

Emiliani, V., Entcheva, E., Hedrich, R., Hegemann, P., Konrad, K.R., Lüscher, C., Mahn, M., Pan, Z.-H., Sims, R.R., Vierock, J. and Yizhar, O. (2022). Optogenetics for light control of biological systems. Nat Rev Methods Primers, 2, 1: 55. doi: 10.1038/s43586-022-00136-4.

Fischer, P., Mukherjee, S., Peter, E., Broser, M., Bartl, F.J., and Hegemann, P. (2021). The inner mechanics of rhodopsin guanylyl cyclase during cGMP-formation revealed by real-time FTIR spectroscopy. Elife, 10, e71384. doi: 10.7554/eLife.71384.

Fischer, P., Schiewer, E., Broser, M., Busse, W., Spreen, A., Grosse, M., Hegemann, P., and Bartl, F. (2023). The functionality of the DC pair in a Rhodopsin Guanylyl Cyclase from Catenaria anguillulae. Journal Mol Biol, 168375. Advance online publication. doi: 10.1016/j.jmb.2023.168375.

Oda, K., Nomura, T., Nakane, T., Yamashita, K., Inoue, K., Ito, S., Vierock, J., Hirata, K., Maturana, A.D., Katayama, K., Ikuta, T., Ishigami, I., Izume, T., Umeda, R., Eguma, R., Oishi, S., Kasuya, G., Kato, T., Kusakizako, T., Shihoya, W., Shimada, H., Takatsuji, T., Takemoto, M., Taniguchi, R., Tomita, A., Nakamura, R., Fukuda, M., Miyauchi, H., Lee, Y., Nango, E., Tanaka, R., Tanaka, T., Sugahara, M., Kimura, T., Shimamura, T., Fujiwara, T., Yamanaka, Y., Owada, S., Joti, Y., Tono, K., Ishitani, R., Hayashi, S., Kandori, H., Hegemann, P., Iwata, S., Kubo, M., Nishizawa, T., and Nureki, O. (2021). Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin. Elife, 10, e62389. doi: 10.7554/eLife.62389.

Rodriguez-Rozada, S., Wietek, J., Tenedini, F., Sauter, K., Dhiman, N., Hegemann, P., Soba, P. and Wiegert, J.S. (2022). Aion is a bistable anion-conducting channelrhodopsin that provides temporally extended and reversible neuronal silencing. Commun Biol, 5, 1: 687. doi: 10.1038/s42003-022-03636-x

Silapetere, A., Hwang, S., Hontani, Y., Fernandez Lahore, R.G., Balke, J., Escobar, F.V., Tros, M., Konold, P.E., Matis, R., Croce, R., Walla, P.J., Hildebrandt, P.Alexiev, U., Kennis, J.T.M., Sun, H., Utesch, T. and Hegemann, P. (2022). QuasAr Odyssey: the origin of fluorescence and its voltage sensitivity in microbial rhodopsins. Nat Commun, 13, 1: 5501. doi: 10.1038/s41467-022-33084-4.


Baumann, T., Schmitt, F. J., Pelzer, A., Spiering, V. J., Freiherr von Sass, G. J., Friedrich, T., Budisa, N. (2018). Engineering 'Golden' Fluorescence by Selective Pressure Incorporation of Non-canonical Amino Acids and Protein Analysis by Mass Spectrometry and Fluorescence. J Vis Exp 134; doi: 10.3791/57017

Friedrich, D., Brünig, F.N., Nieuwkoop, A.J., Netz, R., Hegemann, P. and Oschkinat, H. (2020). Collective exchange processes reveal an active site proton cage in bacteriorhodopsin. Commun. Biol. 3, doi: 10.1038/s42003-019-0733-7.

Fudim, R., Szczepek, M., Vierock, J., Vogt, A., Schmidt, A., Kleinau, G., Fischer, P., Bartl, F., Scheerer, P., Hegemann, P. (2019). Design of a light-gated proton channel based on the crystal structure of Coccomyxa rhodopsin. Sci Signal. 2019 Mar 19;12(573). pii: eaav4203. doi: 10.1126/scisignal.aav4203

Grimm, C., Silapetere, A., Vogt, A., Bernal S., Yinth A., and Hegemann, P. (2018). Electrical properties, substrate specificity and optogenetic potential of the engineered light-driven sodium pump eKR2. Sci Rep 8, 9316; doi: 10.1038/s41598-018-27690-w

Grimm, C., Vierock, J., Hegemann, P., and Wietek, J. (2017). Whole-cell Patch-clamp Recordings for Electrophysiological Determination of Ion Selectivity in Channelrhodopsins. Journal of Visualized Experiments 55497; doi: 10.3791/55497

Kaufmann, J.C.D., Krause B.S., Adam S., Ritter E., Schapiro I., Hegemann P. and Bartl F.J. (2020). Modulation of Light Energy Transfer from Chromophore to Protein in the Channelrhodopsin ReaChR. Biophysical Journal; doi: 10.1016/j.bpj.2020.06.031

Krause, B.S., Grimm, C., Kaufmann, J.C.D., Schneider, F., Sakmar, T.P., Bartl, F.J., and Hegemann, P. (2017). Complex Photochemistry within the Green-Absorbing Channelrhodopsin ReaChR. Biophysical Journal 112, 1166-1175; doi: 10.1016/j.bpj.2017.02.001

Kuhne, J., Vierock, J., Tennigkeit, S., Wietek, J.,  Petersen, D., Dreier, M.-A., Schartner, J., Gavrilijuk, K., Samir, F., El-Mashtoly, S. F., Hegemann, P., and Gerwert, K. (2019). Unifying photocycle model for light adaptation and temporal evolution of cation conductance in Channelrhodopsin-2. Proc Natl Acad Sci USA. 116(19):9380-9389. doi: 10.1073/pnas.1818707116.

Oda, K., Vierock, J., Oishi, S., Rodriguez-Rozada, S., Taniguchi, R., Yamashita, K., Wiegert, J.S., Nishizawa, T., Hegemann, P., Nureki, O. (2018). Crystal structure of the red light-activated channelrhodopsin Chrimson. Nature Comm. 9(1):3949. doi: 10.1038/s41467-018-06421-9.

Oppermann, J., Fischer, P., Silapetere, A., Liepe, B., Rodriguez-Rozada, S., Flores-Uribe, J., Peter, E., Keidel, A., Vierock, J., Kaufmann, J., Broser, M., Luck, M., Bartl, F., Hildebrandt, P., Wiegert, J. S., Béjà, O., Hegemann, P., Wietek, J. (2019). MerMAIDs: A novel family of metagenomically discovered marine anion-conducting and intensely desensitizing channelrhodopsins. Nat Commun. 2019 10(1):3315. doi: 10.1038/s41467-019-11322-6.

Rozenberg, A., Oppermann, J., Wietek, J., Fernandez Lahore, R.G., Sandaa, R.-A., Bratbak, G., Hegemann, P. and Béjà, O. (2020). Lateral Gene Transfer of Anion-Conducting Channelrhodopsins between Green Algae and Giant Viruses. Curr Biol, 30, 24: 4910-4920.e5. doi: 10.1016/j.cub.2020.09.056.

Scheib, U., Broser, M., Constantin, O. M., Yang, S.,Gao, S., Mukherjee, S., Stehfest, K., Nagel, G., Gee, C. E., and Hegemann, P. (2018). Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain. Nature Commun 9, 2046; doi: 10.1038/s41467-018-04428-w

Vierock, J., Grimm, C., Nitzen, N., and Hegemann, P. (2017) Molecular determinants of proton selectivity and gating in the red-light activated channelrhodopsin Chrimson. Sci. Rep. 7:9928; doi: 10.1038/s41598-017-09600-8

Vogt, A., Silapetere, A., Grimm, C., Heiser, F., Möller, M. A., and Hegemann, P. (2019). Engineered Passive Potassium Conductance in the KR2 Sodium Pump. Biophys. J. 116, 1941-1951. doi.org/10.1016/j.bpj.2019.04.001.

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; doi: 10.1038/s41598-017-14330-y

2013 - 2016

AzimiHashemi, N., Erbguth, K., Vogt, A., Riemensperger, T., Rauch, E., Woodmansee, D., Nagpal, J., Brauner, M., Sheves, M., Fiala, A., Kattner, L., Trauner, D., Hegemann, P., Gottschalk, A., and Liewald, J.F. (2014). Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools. Nature Communications 5, 5810.

Berndt, A., Lee, S.Y., Wietek, J., Ramakrishnan, C., Steinberg, E.E., Rashid, A.J., Kim, H., Park, S., Santoro, A., Frankland, P.W., Iyer, S.M., Pak, S., Ahrlund-Richter, S., Delp, S.L., Malenka, R.C., Josselyn, S.A., Carlen, M., Hegemann, P., and Deisseroth, K. (2016). Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity. Proc. Natl. Acad. Sci. U.S.A. 113, 822-829.

Ernst, O.P., Lodowski, D.T., Elstner, M., Hegemann, P., Brown, L.S., and Kandori, H. (2014). Microbial and Animal Rhodopsins: Structures, Functions, and Molecular Mechanisms. Chemical Reviews 114, 126-163.

Kuhne, J., Eisenhauer, K., Ritter, E., Hegemann, P., Gerwert, K., and Bartl, F. (2015). Early Formation of the Ion-Conducting Pore in Channelrhodopsin-2. Angewandte Chemie International Edition 54, 4953-4957.

Richter, F., Scheib, U.S., Mehlhorn, J., Schubert, R., Wietek, J., Gernetzki, O., Hegemann, P., Mathes, T., and Moeglich, A. (2015). Upgrading a microplate reader for photobiology and all-optical experiments. Photochemical & Photobiological Sciences 14, 270-279.

Rost, B.R., Schneider, F., Grauel, M.K., Wozny, C., G Bentz, C., Blessing, A., Rosenmund, T., Jentsch, T.J., Schmitz, D., Hegemann, P., et al. (2015). Optogenetic acidification of synaptic vesicles and lysosomes. Nature Neuroscience 18, 1845-1852.

Scheib, U., Stehfest, K., Gee, C.E., Korschen, H.G., Fudim, R., Oertner, T.G., and Hegemann, P. (2015). The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling. Science Signaling 8, rs8.

Schneider, F., Gradmann, D., and Hegemann, P. (2013). Ion Selectivity and Competition in Channelrhodopsins. Biophysical Journal 105, 91-100.

Schneider, F., Grimm, C., and Hegemann, P. (2015). Biophysics of Channelrhodopsin. Annual Review of Biophysics 44, 167-186.

Vogt, A., Guo, Y., Tsunoda, S.P., Kateriya, S., Elstner, M., and Hegemann, P. (2015). Conversion of a light-driven proton pump into a light-gated ion channel. Scientific Reports 5, 16450.

Vogt, A., Wietek, J., and Hegemann, P. (2013). Gloeobacter Rhodopsin, Limitation of Proton Pumping at High Electrochemical Load. Biophysical Journal 105, 2055-2063.

Wietek, J., Beltramo, R., Scanziani, M., Hegemann, P., Oertner, T.G., and Simon Wiegert, J. (2015). An improved chloride-conducting channelrhodopsin for light-induced inhibition of neuronal activity in vivo. Scientific Reports 5, 14807.

Wietek, J., Broser, M., Krause, B.S., and Hegemann, P. (2016). Identification of a Natural Green Light Absorbing Chloride Conducting Channelrhodopsin from Proteomonas sulcata. J. Biol. Chem. 291, 4121-4127.

Wietek, J., Wiegert, J.S., Adeishvili, N., Schneider, F., Watanabe, H., Tsunoda, S.P., Vogt, A., Elstner, M., Oertner, T.G., and Hegemann, P. (2014). Conversion of channelrhodopsin into a light-gated chloride channel. Science 344, 409-412. [Link to news section.]