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Mechanism of Ion Translocation by Na+-Rhodopsin

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Abstract

This review provides a brief description of the structure and transport function of the recently discovered family of retinal-containing Na+-translocating rhodopsins. The main emphasis is put on the kinetics of generation of electric potential difference in the membrane during a single transporter turnover. According to the proposed transport mechanism of Na+-rhodopsin, the driving force for the Na+ translocation from the cytoplasm is the local electric field created by the H+ movement from the Schiff base.

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Abbreviations

bR:

bacteriorhodopsin

hR:

halorhodopsin

NaR:

Na+-translocating rhodopsin

SB:

Schiff base

ΔΨ:

transmembrane difference in electric potentials

Δp :

proton motive force

References

  1. Blankenship, R. E. (2014) Molecular Mechanisms of Photosynthesis, 2nd Edn., Wiley-Blackwell, Oxford.

  2. Oesterhelt, D., and Stoeckenius, W. (1971) Rhodopsin-like protein from the purple membrane of Halobacterium halobium, Nat. New Biol., 233, 149-152, https://doi.org/10.1038/newbio233149a0.

    Article  CAS  PubMed  Google Scholar 

  3. Oesterhelt, D., and Stoeckenius, W. (1973) Functions of a new photoreceptor membrane, Proc. Natl. Acad. Sci. USA, 70, 2853-2857, https://doi.org/10.1073/pnas.70.10.2853.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Luecke, H., Richter, H. T., and Lanyi, J. K. (1998) Proton transfer pathways in bacteriorhodopsin at 2.3 angstrom resolution, Science, 280, 1934-1937, https://doi.org/10.1126/science.280.5371.1934.

    Article  CAS  PubMed  Google Scholar 

  5. Ernst, O. P., Lodowski, D. T., Elstner, M., Hegemann, P., Brown, L. S., et al. (2014) Microbial and animal rhodopsins: structures, functions, and molecular mechanisms, Chem. Rev., 114, 126-163, https://doi.org/10.1021/cr4003769.

    Article  CAS  PubMed  Google Scholar 

  6. Matsuno-Yagi, A., and 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, https://doi.org/10.1016/0006-291x(77)91245-1.

    Article  CAS  PubMed  Google Scholar 

  7. Schobert, B., and Lanyi, J. K. (1982) Halorhodopsin is a light-driven chloride pump, J. Biol. Chem., 257, 10306-10313, https://doi.org/10.1016/S0021-9258(18)34020-1.

    Article  CAS  PubMed  Google Scholar 

  8. Kolbe, M., Besir, H., Essen, L. O., and Oesterhelt, D. (2000) Structure of the light-driven chloride pump halorhodopsin at 1.8 Å resolution, Science, 288, 1390-1396, https://doi.org/10.1126/science.288.5470.1390.

    Article  CAS  PubMed  Google Scholar 

  9. Kalaidzidis, I. V., Kalaidzidis, Y. L., and Kaulen, A. D. (1998) Flash-induced voltage changes in halorhodopsin from Natronobacterium pharaonis, FEBS Lett., 427, 59-63, https://doi.org/10.1016/s0014-5793(98)00394-9.

    Article  CAS  PubMed  Google Scholar 

  10. Sasaki, J., Brown, L. S., Chon, Y. S., Kandori, H., Maeda, A., et al. (1995) Conversion of bacteriorhodopsin into a chloride ion pump, Science, 269, 73-75, https://doi.org/10.1126/science.7604281.

    Article  CAS  PubMed  Google Scholar 

  11. Béjà, O., Spudich, E. N., Spudich, J. L., Leclerc, M., DeLong, E. F. (2001) Proteorhodopsin phototrophy in the ocean, Nature, 411, 786-789, https://doi.org/10.1038/35081051.

    Article  PubMed  Google Scholar 

  12. Inoue, K., Ono, H., Abe-Yoshizumi, R., Yoshizawa, S., Ito, H., et al. (2013) A light-driven sodium ion pump in marine bacteria, Nat. Commun., 4, 1678, https://doi.org/10.1038/ncomms2689.

    Article  CAS  PubMed  Google Scholar 

  13. Kwon, S. K., Kim, B. K., Song, J. Y., Kwak, M. J., Lee, C. H., et al. (2013) Genomic makeup of the marine flavobacterium Nonlabens (Donghaeana) dokdonensis and identification of a novel class of rhodopsins, Genome Biol. Evol., 5, 187-199, https://doi.org/10.1093/gbe/evs134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Balashov, S. P., Imasheva, E. S., Dioumaev, A. K., Wang, J. M., Jung, K. H., et al. (2014) Light-driven Na+ pump from Gillisia limnaea: a high-affinity Na+ binding site is formed transiently in the photocycle, Biochemistry, 53, 7549-7561, https://doi.org/10.1021/bi501064n.

    Article  CAS  PubMed  Google Scholar 

  15. Bertsova, Y. V., Bogachev, A. V., and Skulachev, V. P. (2015) Proteorhodopsin from Dokdonia sp. PRO95 is a light-driven Na+-pump, Biochemistry (Moscow), 80, 449-454, https://doi.org/10.1134/S0006297915040082.

    Article  CAS  Google Scholar 

  16. Li, H., Sineshchekov, O. A., da Silva, G. F., and Spudich, J. L. (2015) In vitro demonstration of dual light-driven Na+/H+ pumping by a microbial rhodopsin, Biophys. J., 109, 1446-1453, https://doi.org/10.1016/j.bpj.2015.08.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tsunoda, S. P., Prigge, M., Abe-Yoshizumi, R., Inoue, K., Kozaki, Y., et al. (2017) Functional characterization of sodium-pumping rhodopsins with different pumping properties, PLoS One, 12, e0179232, https://doi.org/10.1371/journal.pone.0179232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gushchin, I., Shevchenko, V., Polovinkin, V., Kovalev, K., Alekseev, A., et al. (2015) Crystal structure of a light-driven sodium pump, Nat. Struct. Mol. Biol., 22, 390-395, https://doi.org/10.1038/nsmb.3002.

    Article  CAS  PubMed  Google Scholar 

  19. Kato, H. E., Inoue, K., Abe-Yoshizumi, R., Kato, Y., Ono, H., et al. (2015) Structural basis for Na+ transport mechanism by a light-driven Na+ pump, Nature, 521, 48-53, https://doi.org/10.1038/nature14322.

    Article  CAS  PubMed  Google Scholar 

  20. Shibata, M., Inoue, K., Ikeda, K., Konno, M., Singh, M., et al. (2018) Oligomeric states of microbial rhodopsins determined by high-speed atomic force microscopy and circular dichroic spectroscopy, Sci. Rep., 8, 8262, https://doi.org/10.1038/s41598-018-26606-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Otomo, A., Mizuno, M., Inoue, K., Kandori, H., and Mizutani, Y. (2020) Allosteric communication with the retinal chromophore upon ion binding in a light-driven sodium ion-pumping rhodopsin, Biochemistry, 59, 520-529, https://doi.org/10.1021/acs.biochem.9b01062.

    Article  CAS  PubMed  Google Scholar 

  22. Skulachev, V. P. (1993) Interrelations of bioenergetic and sensory functions of the retinal proteins, Q. Rev. Biophys., 26, 177-199, https://doi.org/10.1017/s0033583500004066.

    Article  CAS  PubMed  Google Scholar 

  23. Weinert, T., Skopintsev, P., James, D., Dworkowski, F., Panepucci, E., et al. (2019) Proton uptake mechanism in bacteriorhodopsin captured by serial synchrotron crystallography, Science, 365, 61-65, https://doi.org/10.1126/science.aaw8634.

    Article  CAS  PubMed  Google Scholar 

  24. Inoue, K., Nomura, Y., and Kandori, H. (2016) Asymmetric functional conversion of eubacterial light-driven ion pumps, J. Biol. Chem., 291, 9883-9893, https://doi.org/10.1074/jbc.M116.716498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Matsuo, J., Kikukawa, T., Fujisawa, T., Hoff, W. D., and Unno, M. (2020) “Watching” a molecular twist in a protein by Raman optical activity, J. Phys. Chem. Lett., 11, 8579-8584, https://doi.org/10.1021/acs.jpclett.0c02448.

    Article  CAS  PubMed  Google Scholar 

  26. Luecke, H., Schobert, B., Stagno, J., Imasheva, E. S., Wang, J. M., et al. (2008) Crystallographic structure of xanthorhodopsin, the light-driven proton pump with a dual chromophore, Proc. Natl. Acad. Sci. USA, 105, 16561-16565, https://doi.org/10.1073/pnas.0807162105.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Balashov, S. P., Imasheva, E. S., Wang, J. M., and Lanyi, J. K. (2008) Excitation energy-transfer and the relative orientation of retinal and carotenoid in xanthorhodopsin, Biophys. J., 95, 2402-2414, https://doi.org/10.1529/biophysj.108.132175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bertsova, Y. V., Arutyunyan, A. M., and Bogachev, A. V. (2016) Na+-translocating rhodopsin from Dokdonia sp. PRO95 does not contain carotenoid antenna, Biochemistry (Moscow), 81, 414-419, https://doi.org/10.1134/S000629791604012X.

    Article  CAS  Google Scholar 

  29. Anashkin, V. A., Bertsova, Y. V., Mamedov, A. M., Mamedov, M. D., Arutyunyan, A. M., et al. (2018) Engineering a carotenoid-binding site in Dokdonia sp. PRO95 Na+-translocating rhodopsin by a single amino acid substitution, Photosynth. Res., 136, 161-169, https://doi.org/10.1007/s11120-017-0453-0.

    Article  CAS  PubMed  Google Scholar 

  30. Tahara, S., Takeuchi, S., Abe-Yoshizumi, R., Inoue, K., Ohtani, H., et al. (2015) Ultrafast photoreaction dynamics of a light-driven sodium-ion-pumping retinal protein from Krokinobacter eikastus revealed by femtosecond time-resolved absorption spectroscopy, J. Phys. Chem. Lett., 6, 4481-4486, https://doi.org/10.1021/acs.jpclett.5b01994.

    Article  CAS  PubMed  Google Scholar 

  31. Miranda, M. R., Choi, A. R., Shi, L., Bezerra, A. G. Jr., Jung, K. H., et al. (2009) The photocycle and proton translocation pathway in a cyanobacterial ion-pumping rhodopsin, Biophys. J., 96, 1471-1481, https://doi.org/10.1016/j.bpj.2008.11.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Morizumi, T., Ou, W. L., Van Eps, N., Inoue, K., Kandori, H., et al. (2019) X-ray crystallographic structure and oligomerization of Gloeobacter rhodopsin, Sci. Rep., 9, 11283, https://doi.org/10.1038/s41598-019-47445-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bogachev, A. V., Bertsova, Y. V., Verkhovskaya, M. L., Mamedov, M. D., and Skulachev, V. P. (2016) Real-time kinetics of electrogenic Na+ transport by rhodopsin from the marine flavobacterium Dokdonia sp. PRO95, Sci. Rep., 6, 21397, https://doi.org/10.1038/srep21397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nango, E., Royant, A., Kubo, M., Nakane, T., Wickstrand, C., et al. (2016) A three-dimensional movie of structural changes in bacteriorhodopsin, Science, 354, 1552-1557, https://doi.org/10.1126/science.aah3497.

    Article  CAS  PubMed  Google Scholar 

  35. Grandjean, J., Laszlo, P., and Gerday, C. (1977) Sodium complexation by the calcium binding site of parvalbumin, FEBS Lett., 81, 376-380, https://doi.org/10.1016/0014-5793(77)80558-9.

    Article  CAS  PubMed  Google Scholar 

  36. Monoi, H. (1985) Nuclear magnetic resonance of 23Na ions interacting with the gramicidin channel, Biophys. J., 48, 643-662, https://doi.org/10.1016/S0006-3495(85)83820-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bogachev, A. V., Bertsova, Y. V., Aitio, O., Permi, P., and Verkhovsky, M. I. (2007) Redox-dependent sodium binding by the Na+-translocating NADH:quinone oxidoreductase from Vibrio harveyi, Biochemistry, 46, 10186-10191, https://doi.org/10.1021/bi700440w.

    Article  CAS  PubMed  Google Scholar 

  38. Jakdetchai, O., Eberhardt, P., Asido, M., Kaur, J., Kriebel, C. N., et al. (2021) Probing the photointermediates of light-driven sodium ion pump Kr2 by DNP-enhanced solid-state NMR, Sci. Adv., 7, eabf4213, https://doi.org/10.1126/sciadv.abf4213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kovalev, K., Astashkin, R., Gushchin, I., Orekhov, P., Volkov, D., et al. (2020) Molecular mechanism of light-driven sodium pumping, Nat. Commun., 11, 2137, https://doi.org/10.1038/s41467-020-16032-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Murabe, K., Tsukamoto, T., Aizawa, T., Demura, M., and Kikukawa, T. (2020) Direct detection of the substrate uptake and release reactions of the light-driven sodium-pump rhodopsin, J. Am. Chem. Soc., 142, 16023-16030, https://doi.org/10.1021/jacs.0c07264.

    Article  CAS  PubMed  Google Scholar 

  41. Skopintsev, P., Ehrenberg, D., Weinert, T., James, D., Kar, R. K., et al. (2020) Femtosecond-to-millisecond structural changes in a light-driven sodium pump, Nature, 583, 314-318, https://doi.org/10.1038/s41586-020-2307-8.

    Article  CAS  PubMed  Google Scholar 

  42. Konno, M., Kato, Y., Kato, H. E., Inoue, K., Nureki, O., Kandori, H. (2016) Mutant of a light-driven sodium ion pump can transport cesium ions, J. Phys. Chem. Lett., 7, 51-55, https://doi.org/10.1021/acs.jpclett.5b02385.

    Article  CAS  PubMed  Google Scholar 

  43. Mamedov, A. M., Bertsova, Y. V., Anashkin, V. A., Mamedov, M. D., Baykov, A. A., et al. (2018) Identification of the key determinant of the transport promiscuity in Na+-translocating rhodopsins, Biochem. Biophys. Res. Commun., 499, 600-604, https://doi.org/10.1016/j.bbrc.2018.03.196.

    Article  CAS  PubMed  Google Scholar 

  44. Kato, Y., Inoue, K., and Kandori, H. (2015) Kinetic analysis of H+-Na+ selectivity in a light-driven Na+-pumping rhodopsin, J. Phys. Chem. Lett., 6, 5111-5115, https://doi.org/10.1021/acs.jpclett.5b02371.

    Article  CAS  PubMed  Google Scholar 

  45. Nakamura, T., Kawasaki, S., and Unemoto, T. (1992) Roles of K+ and Na+ in pH homeostasis and growth of the marine bacterium Vibrio alginolyticus, J. Gen. Microbiol., 138, 1271-1276, https://doi.org/10.1099/00221287-138-6-1271.

    Article  CAS  PubMed  Google Scholar 

  46. Kandori, H., Inoue, K., and Tsunoda, S. P. (2018) Light-driven sodium-pumping rhodopsin: a new concept of active transport, Chem. Rev., 118, 10646-10658, https://doi.org/10.1021/acs.chemrev.7b00548.

    Article  CAS  PubMed  Google Scholar 

  47. Parsegian, A. (1969) Energy of an ion crossing a low dielectric membrane: solutions to four relevant electrostatic problems, Nature, 221, 844-846, https://doi.org/10.1038/221844a0.

    Article  CAS  PubMed  Google Scholar 

  48. Mitchell, R., Mitchell, P., and Rich, P. R. (1992) Protonation states of the catalytic intermediates of cytochrome c oxidase, Biochim. Biophys. Acta, 1101, 188-191, https://doi.org/10.1016/0005-2728(92)90221-M.

    Article  CAS  PubMed  Google Scholar 

  49. Popović, D. M., and Stuchebrukhov, A. A. (2004) Proton pumping mechanism and catalytic cycle of cytochrome c oxidase: coulomb pump model with kinetic gating, FEBS Lett., 566, 126-130, https://doi.org/10.1016/j.febslet.2004.04.016.

    Article  CAS  PubMed  Google Scholar 

  50. Bogachev, A. V., and Verkhovsky, M. I. (2005) Na+-translocating NADH:quinone oxidoreductase: progress achieved and prospects of investigations, Biochemistry (Moscow), 70, 143-149, https://doi.org/10.1007/s10541-005-0093-4.

    Article  CAS  Google Scholar 

  51. Dracheva, S. M., Drachev, L. A., Konstantinov, A. A., Semenov, A. Yu., Skulachev, V. P., et al. (1988) Electrogenic steps in the redox reactions catalyzed by photosynthetic reaction-centre complex from Rhodopseudomonas viridis, Eur. J. Biochem., 171, 253-264, https://doi.org/10.1111/j.1432-1033.

    Article  CAS  PubMed  Google Scholar 

  52. Konstantinov, A. A., Siletsky, S., Mitchell, D., Kaulen, A., and Gennis, R. B. (1997) The roles of the two proton input channels in cytochrome c oxidase from Rhodobacter sphaeroides probed by the effects of site-directed mutations on time-resolved electrogenic intraprotein proton transfer, Proc. Natl. Acad. Sci. USA, 94, 9085-9090, https://doi.org/10.1073/pnas.94.17.9085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kaulen, A. D. (2000) Electrogenic processes and protein conformational changes accompanying the bacteriorhodopsin photocycle, Biochim. Biophys. Acta, 1460, 204-219, https://doi.org/10.1016/s0005-2728(00)00140-7.

    Article  CAS  PubMed  Google Scholar 

  54. Siletsky, S. A., Mamedov, M. D., Lukashev, E. P., Balashov, S. P., Dolgikh, D. A., et al. (2016) Electrogenic steps of light-driven proton transport in ESR, a retinal protein from Exiguobacterium sibiricum, Biochim. Biophys. Acta, 1857, 1741-1750, https://doi.org/10.1016/j.bbabio.2016.08.004.

    Article  CAS  PubMed  Google Scholar 

  55. Mamedov, M. D., Mamedov, A. M., Bertsova, Y. V., and Bogachev, A. V. (2016) A single mutation converts bacterial Na+-transporting rhodopsin into an H+ transporter, FEBS Lett., 590, 2827-2835, https://doi.org/10.1002/1873-3468.12324.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Inoue, K. (2021) Diversity, mechanism, and optogenetic application of light-driven ion pump rhodopsins, Adv. Exp. Med. Biol., 1293, 89-126, https://doi.org/10.1007/978-981-15-8763-4_6.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation, Agreement no. 075-15-2021-1354 from October 7, 2021.

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Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234, Moscow, Russia

    Alexander V. Bogachev, Alexander A. Baykov, Yulia V. Bertsova & Mahir D. Mamedov

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  1. Alexander V. Bogachev
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  2. Alexander A. Baykov
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  3. Yulia V. Bertsova
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Contributions

A. V. Bogachev and A. A. Baykov wrote the paper, Y. V. Bertsova and M. D. Mamedov prepared figures and participated in discussion. All authors read and approved the final version of the paper.

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Correspondence to Alexander V. Bogachev.

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The authors declare no conflicts of interests in financial or any other sphere. This article does not contain description of studies with human participants or animals performed by any of the authors.

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Bogachev, A.V., Baykov, A.A., Bertsova, Y.V. et al. Mechanism of Ion Translocation by Na+-Rhodopsin. Biochemistry Moscow 87, 731–741 (2022). https://doi.org/10.1134/S0006297922080053

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