[PDF]    https://doi.org/10.3952/physics.v62i3.4801

Open access article / Atviros prieigos straipsnis
Lith. J. Phys. 62, 179–193 (2022)

MECHANISM OF PROTON TRANSFER IN BACTERIORHODOPSIN
Mindaugas Macernisa, Lev Mourokhb, Ligitas Vinciunasa, and Leonas Valkunasa,c
a Institute of Chemical Physics, Faculty of Physics, Vilnius University, Saulėtekio 9-III, 10222 Vilnius, Lithuania
b Department of Physics, Queens College of the City University of New York, Flushing, 11367 New York, USA
c Department of Molecular Compound Physics, Center for Physical Sciences and Technology, Saulėtekio 3, 10257 Vilnius, Lithuania
Email: leonas.valkunas@ff.vu.lt

Received 22 June 2022; accepted 3 July 2022

Photoinduced proton pumping in bateriorhodopsin (bR) was extensively studied using multiple experimental methods and utilizing various theoretical modelling approaches. These studies usually refer to the well-resolved structural data of bacteriorhodopsin. However, despite the obtained results, the origin of the proton pumping force initiated by the electronic excitation of retinal remains questionable. Using quantum chemical calculations, we have revealed that the retinal molecule after its excitation is fixed in the ground state of 13-cis,15-syn configuration, as a result of interaction with specific protein residuals. Reaching this fixed configuration, the proton is first transferred to the aspartic acid No. 85 (Asp-85) residue from the water molecule, which is subsequently restored by the proton initially located in the Schiff base. We discuss the challenges and approaches to modelling the proton transfer in bR and demonstrate that the process, which starts from the electronic excitation of the retinal molecule, is mainly due to the detailed arrangement of the protein environment.
Keywords: photoinduced proton transfer, membrane proteins, bacteriorhodopsin, retinal, isomerization
PACS: 87.14.ep, 77.65.-j, 82.80.Yc, 83.10.Rs, 03.65.-w


PROTONO PERNAŠOS MECHANIZMAS BAKTERIORODOPSINE
Mindaugas Mačernisa, Lev Mourokhb, Ligitas Vinciūnasa, and Leonas Valkūnasa,c

a Vilniaus universiteto Fizikos fakulteto Cheminės fizikos institutas, Vilnius, Lietuva
b Niujorko miesto universiteto Kvinso koledžo Fizikos skyrius, Niujorkas, JAV
c Fizinių ir technologijos mokslų centro Molekulinių darinių fizikos skyrius, Vilnius, Lietuva
Bakteriorodopsine (BR) vykstanti protono pernaša plačiai nagrinėjama daugeliu eksperimentiniais ir teoriniais metodais. Pastarieji tyrimai paremti ypač detaliais kristalografiniais BR duomenimis. Vis dėlto, nepaisant turimų duomenų, retinalyje vykstanti protono pernaša, inicijuota elektroninio sužadinimo, nėra visiškai aiški. Naudodami kvantinės chemijos skaičiavimus, nagrinėjome retinalio molekulę, kuri yra fiksuota 13-cis,15-syn konfigūracijos pagrindinėje būsenoje ir susidaro dėl baltyminės aplinkos įtakos. Naudodami šią fiksuotą būseną, nustatėme, kad protono pernaša į asparto rūgštį Nr. 85 (Asp-85) vyksta tarpininkaujant vandens molekulei, o analogiškoje aplinkoje taip pat dalyvaujama vėl protonuojant Šifo bazę. Aptarėme BR vykstančio protonų perdavimo modeliavimo iššūkius ir metodus, analizuodami procesą, kai molekulės elektroninio sužadinimo savybes nulemia baltyminė aplinka.


References / Nuorodos

[1] D. Oesterhelt and W. Stoeckenius, Rhodopsin-like protein from the purple membrane of Halobacterium halobium, Nat. New. Biol. 233, 149–152 (1971),
https://doi.org/10.1038/newbio233149a0
[2] R.F. Peck, S. DasSarma, and M.P. Krebs, Homologous gene knockout in the archaeon Halobacterium salinarum with ura3 as a counterselectable marker, Mol. Microbiol. 35, 667–676 (2000),
https://doi.org/10.1046/j.1365-2958.2000.01739.x
[3] N. Grigorieff, T.A. Ceska, K.H. Downing, J.M. Baldwin, and R. Henderson, Electron-crystallographic refinement of the structure of bacteriorhodopsin, J. Mol. Biol. 259, 393–421 (1996),
https://doi.org/10.1006/jmbi.1996.0328
[4] U.N. Morzan, D.J. Alonso de Armino, N.O. Foglia, F. Ramirez, M.C. Gonzalez Lebrero, D.A. Scherlis, and D.A. Estrin, Spectroscopy in complex environments from QM–MM simulations, Chem. Rev. 118, 4071–4113 (2018),
https://doi.org/10.1021/acs.chemrev.8b00026
[5] H. Luecke, B. Schobert, H.T. Richter, J.P. Cartailler, and J.K. Lanyi, Structure of bacteriorhodopsin at 1.55 A resolution, J. Mol. Biol. 291, 899–911 (1999),
https://doi.org/10.1006/jmbi.1999.3027
[6] L. Essen, R. Siegert, W.D. Lehmann, and D. Oesterhelt, Lipid patches in membrane protein oligomers: crystal structure of the bacteriorhodopsin-lipid complex, Proc. Natl. Acad. Sci. U. S. A. 95, 11673–11678 (1998),
https://doi.org/10.1073/pnas.95.20.11673
[7] U. Haupts, J. Tittor, and D. Oesterhelt, Closing inon bacteriorhodopsin: progress in understanding the molecule, Annu. Rev. Biophys. Biomol. Struct. 28, 367–399 (1999),
https://doi.org/10.1146/annurev.biophys.28.1.367
[8] J.K. Lanyi, Molecular mechanism of ion transport in bacteriorhodopsin: Insights from crystallographic, spectroscopic, kinetic, and mutational studies, J. Phys. Chem. B 104, 11441–11448 (2000),
https://doi.org/10.1021/jp0023718
[9] J.K. Lanyi, Bacteriorhodopsin, Annu. Rev. Physiol. 66, 665–688 (2004),
https://doi.org/10.1146/annurev.physiol.66.032102.150049
[10] J.K. Lanyi, Proton transfers in the bacteriorhodopsin photocycle, Biochim. Biophys. Acta 1757, 1012–1018 (2006),
https://doi.org/10.1016/j.bbabio.2005.11.003
[11] A. Kawanabe, Y. Furutani, K.H. Jung, and H. Kandori, Photochromism of Anabaena sensory rhodopsin, J. Am. Chem. Soc. 129, 8644–8649 (2007),
https://doi.org/10.1021/ja072085a
[12] H. Kandori, Ion-pumping microbial rhodopsins, Front. Mol. Biosci. 2, 52 (2015),
https://doi.org/10.3389/fmolb.2015.00052
[13] C. Wickstrand, R. Dods, A. Royant, and R. Neutze, Bacteriorhodopsin: Would the real structural intermediates please stand up?, Biochim. Biophys. Acta Gen. Subj. 1850, 536–553 (2015),
https://doi.org/10.1016/j.bbagen.2014.05.021
[14] L.S. Brown, L. Bonet, R. Needleman, and J.K. Lanyi, Estimated acid dissociation constants of the Schiff base, Asp-85, and Arg-82 during the bacteriorhodopsin photocycle, Biophys. J. 65, 124–130 (1993),
https://doi.org/10.1016/S0006-3495(93)81064-6
[15] A. Accardi and C. Miller, Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels, Nature 427, 803–807 (2004),
https://doi.org/10.1038/nature02314
[16] Y. Guo, F.E. Beyle, B.M. Bold, H.C. Watanabe, A. Koslowski, W. Thiel, P. Hegemann, M. Marazzi, and M. Elstner, Active site structure and absorption spectrum of channelrhodopsin-2 wild-type and C128T mutant, Chem. Sci. 7, 3879–3891 (2016),
https://doi.org/10.1039/C6SC00468G
[17] A.Y. Smirnov, L.G. Mourokh, and F. Nori, Kinetics of proton pumping in cytochrome c oxidase, J. Chem. Phys. 130, 235105 (2009),
https://doi.org/10.1063/1.3155213
[18] L. Mourokh and M. Vittadello, Physical model of proton-pumping Q-cycle in respiratory and photosynthetic electron transport chains, Chem. Phys. 530, 110638 (2020),
https://doi.org/10.1016/j.chemphys.2019.110638
[19] A. Onufriev, A. Smondyrev, and D. Bashford, Proton affinity changes driving unidirectional proton transport in the bacteriorhodopsin photocycle, J. Mol. Biol. 332, 1183–1193 (2003),
https://doi.org/10.1016/S0022-2836(03)00903-3
[20] N. Calimet and G. Matthias Ullmann, The influence of a transmembrane pH gradient on protonation probabilities of bacteriorhodopsin: The structural basis of the back-pressure effect, J. Mol. Biol. 339, 571–589 (2004),
https://doi.org/10.1016/j.jmb.2004.03.075
[21] R.B. Gennis and T.G. Ebrey, Proton pump caught in the act, Science 286, 252–253 (1999),
https://doi.org/10.1126/science.286.5438.252
[22] H. Luecke, B. Schobert, H.T. Richter, J.P. Cartailler, and J.K. Lanyi, Structural changes in bacteriorhodopsin during ion transport at 2 angstrom resolution, Science 286, 255–260 (1999),
https://doi.org/10.1126/science.286.5438.255
[23] E. Nango, A. Royant, M. Kubo, T. Nakane, C. Wickstrand, T. Kimura, T. Tanaka, K. Tono, C. Song, R. Tanaka, et al., A three-dimensional movie of structural changes in bacteriorhodopsin, Science 354, 1552–1557 (2016),
https://doi.org/10.2210/pdb5b6v/pdb
[24] D. Bashford and M. Karplus, Multiple-site titration curves of proteins: an analysis of exact and approximate methods for their calculation, J. Phys. Chem. B 95, 9556–9561 (1991),
https://doi.org/10.1021/j100176a093
[25] J. Iles-Smith, N. Lambert, and A. Nazir, Environmental dynamics, correlations, and the emergence of noncanonical equilibrium states in open quantum systems, Phys. Rev. A 90, 032114 (2014),
https://doi.org/10.1103/PhysRevA.90.032114
[26] J. Iles-Smith, A.G. Dijkstra, N. Lambert, and A. Nazir, Energy transfer in structured and unstructured environments: Master equations beyond the Born-Markov approximations, J. Chem. Phys. 144, 044110 (2016),
https://doi.org/10.1063/1.4940218
[27] B.P. Kietis, M. Mačernis, J. Šulskus, and L. Valkūnas, Estimation of the permanent dipole moment of bacteriorhodopsin, Lith. J. Phys. 50, 451–462 (2010),
https://doi.org/10.3952/lithjphys.50404
[28] B.F.E. Curchod and T.J. Martínez, Ab initio nonadiabatic quantum molecular dynamics, Chem. Rev. 118, 3305–3336 (2018),
https://doi.org/10.1021/acs.chemrev.7b00423
[29] J.K. Yu, R. Liang, F. Liu, and T.J. Martínez, First-principles characterization of the elusive I fluorescent state and the structural evolution of retinal protonated Schiff base in bacteriorhodopsin, J. Am. Chem. Soc. 141, 18193–18203 (2019),
https://doi.org/10.1021/jacs.9b08941
[30] C. Lee, S. Sekharan, and B. Mertz, Theoretical insights into the mechanism of wavelength regulation in blue-absorbing proteorhodopsin, J. Phys. Chem. B 123, 10631–10641 (2019),
https://doi.org/10.1021/acs.jpcb.9b08189
[31] R. Tripathi, H. Forbert, and D. Marx, Settling the long-standing debate on the proton storage site of the prototype light-driven proton pump bacteriorhodopsin, J. Phys. Chem. B 123, 9598–9608 (2019),
https://doi.org/10.1021/acs.jpcb.9b09608
[32] Y. Guo, F.E. Wolff, I. Schapiro, M. Elstner, and M. Marazzi, Different hydrogen bonding environments of the retinal protonated Schiff base control the photoisomerization in channelrhodopsin-2, Phys. Chem. Chem. Phys. 20, 27501–27509 (2018),
https://doi.org/10.1039/C8CP05210G
[33] Y. Zhang, P. Xie, X. He, and K. Han, High-efficiency microiterative optimization in QM/MM simulations of large flexible systems, J. Chem. Theory Comput. 12, 4632–4643 (2016),
https://doi.org/10.1021/acs.jctc.6b00547
[34] S. Hayashi and I. Ohmine, Proton transfer in bacteriorhodopsin: structure, excitation, IR spectra, and potential energy surface analyses by an ab initio QM/MM method, J. Phys. Chem. B 104, 10678–10691 (2000),
https://doi.org/10.1021/jp001508r
[35] S. Hayashi, E. Tajkhorshid, and K. Schulten, Molecular dynamics simulation of bacteriorhodopsin's photoisomerization using ab initio forces for the excited chromophore, Biophys. J. 85, 1440–1449 (2003),
https://doi.org/10.1016/S0006-3495(03)74576-7
[36] C. Punwong, J. Owens, and T.J. Martínez, Direct QM/MM excited-state dynamics of retinal protonated Schiff base in isolation and methanol solution, J. Phys. Chem. B. 119, 704–714 (2015),
https://doi.org/10.1021/jp5038798
[37] J.-Y. Hasegawa, K.J. Fujimoto, and T. Kawatsu, A configuration interaction picture for a molecular environment using localized molecular orbitals: The excited states of retinal proteins, J. Chem. Theory Comput. 8, 4452–4461 (2012),
https://doi.org/10.1021/ct300510b
[38] S. Zhu, M.F. Brown, and S.E. Feller, Retinal conformation governs pKa of protonated Schiff base in rhodopsin activation, J. Am. Chem. Soc. 135, 9391–9398 (2013),
https://doi.org/10.1021/ja4002986
[39] N.J.A. Coughlan, K.J. Catani, B.D. Adamson, U. Wille, and E.J. Bieske, Photoisomerization action spectrum of retinal protonated Schiff base in the gas phase, J. Chem. Phys. 140, 164307 (2014),
https://doi.org/10.1063/1.4871883
[40] M. Huix-Rotllant, M. Filatov, S. Gozem, I. Schapiro, M. Olivucci, and N. Ferré, Assessment of density functional theory for describing the correlation effects on the ground and excited state potential energy surfaces of a retinal chromophore model, J. Chem. Theory Comput. 9, 3917–3932 (2013),
https://doi.org/10.1021/ct4003465
[41] A.-N. Bondar, M. Elstner, S. Suhai, J.C. Smith, and S. Fischer, Mechanism of primary proton transfer in bacteriorhodopsin, Structure 12, 1281–1288 (2004),
https://doi.org/10.1016/j.str.2004.04.016
[42] A.-N. Bondar, S. Fischer, J.C. Smith, M. Elstner, and S. Suhai, Key role of electrostatic interactions in bacteriorhodopsin proton transfer, J. Am. Chem. Soc. 126, 14668–14677 (2004),
https://doi.org/10.1021/ja047982i
[43] K. Edman, A. Royant, G. Larsson, F. Jacobson, T. Taylor, D. van der Spoel, E.M. Landau, E. Pebay-Peyroula, and R. Neutze, Deformation of helix C in the low temperature L-intermediate of bacteriorhodopsin, J. Biol. Chem. 279, 2147–2158 (2004),
https://doi.org/10.1074/jbc.M300709200
[44] G. Mathias and D. Marx, Structures and spectral signatures of protonated water networks in bacteriorhodopsin, Proc. Natl. Acad. Sci. 104, 6980–6985 (2007),
https://doi.org/10.1073/pnas.0609229104
[45] S. Gozem, P.J.M. Johnson, A. Halpin, H.L. Luk, T. Morizumi, V.I. Prokhorenko, O.P. Ernst, M. Olivucci, and R.J.D. Miller, Excited-state vibronic dynamics of bacteriorhodopsin from two-dimensional electronic photon echo spectroscopy and multiconfigurational quantum chemistry, J. Phys. Chem. Lett. 11, 3889–3896 (2020),
https://doi.org/10.1021/acs.jpclett.0c01063
[46] D. Friedrich, F.N. Brünig, A.J. Nieuwkoop, R.R. Netz, P. Hegemann, and H. Oschkinat, Collective exchange processes reveal an active site proton cage in bacteriorhodopsin, Commun. Biol. 3, 4 (2020),
https://doi.org/10.1038/s42003-019-0733-7
[47] G. Nass Kovacs, J.-P. Colletier, M.L. Grünbein, Y. Yang, T. Stensitzki, A. Batyuk, S. Carbajo, R.B. Doak, D. Ehrenberg, L. Foucar, et al., Three-dimensional view of ultrafast dynamics in photoexcited bacteriorhodopsin, Nat. Commun. 10, 3177 (2019),
https://doi.org/10.1038/s41467-019-10758-0
[48] V.R.I. Kaila, R. Send, and D. Sundholm, The effect of protein environment on photoexcitation properties of retinal, J. Phys. Chem. B. 116, 2249–2258 (2012),
https://doi.org/10.1021/jp205918m
[49] M. Macernis, J. Sulskus, C.D.P. Duffy, A.V. Ruban, and L. Valkunas, Electronic spectra of structurally deformed lutein, J. Phys. Chem. A. 116, 9843–9853 (2012),
https://doi.org/10.1021/jp304363q
[50] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, G.A. Petersson, H. Nakatsuji, et al., Gaussian 16, Revision C.01, Wallingford, CT (2016)
[51] D. Oesterhelt, The structure and mechanism of the family of retinal proteins from halophilic archaea, Curr. Opin. Struct. Biol. 8, 489–500 (1998),
https://doi.org/10.1016/S0959-440X(98)80128-0
[52] J.K. Lanyi, Proton translocation mechanism and energetics in the light-driven pump bacteriorhodopsin, Biochim. Biophys. Acta Bioenerg. 1183, 241–261 (1993),
https://doi.org/10.1016/0005-2728(93)90226-6
[53] J.K. Lanyi, Mechanism of ion transport across membranes. Bacteriorhodopsin as a prototype for proton pumps, J. Biol. Chem. 272, 31209–31212 (1997),
https://doi.org/10.1074/jbc.272.50.31209
[54] S.P. Balashov, E.S. Imasheva, R. Govindjee, M. Sheves, and T.G. Ebrey, Evidence that aspartate-85 has a higher pKa in all-trans than in 13-cisbacteriorhodopsin, Biophys. J. 71, 1973–1984 (1996),
https://doi.org/10.1016/S0006-3495(96)79395-5
[55] R. Rammelsberg, G. Huhn, M. Lübben, and K. Gerwert, Bacteriorhodopsin's intramolecular proton-release pathway consists of a hydrogen-bondednetwork, Biochemistry 37, 5001–5009 (1998),
https://doi.org/10.1021/bi971701k
[56] H. Luecke, H.T. Richter, and J.K. Lanyi, Proton transfer pathways in bacteriorhodopsin at 2.3 angstrom resolution, Science 280, 1934–1937 (1998),
https://doi.org/10.1126/science.280.5371.1934
[57] H.-T. Richter, L.S. Brown, R. Needleman, and J.K. Lanyi, A linkage of the pKa's of asp-85 and glu-204 forms part of the reprotonation switch of bacteriorhodopsin, Biochemistry 35, 4054–4062 (1996),
https://doi.org/10.1021/bi952883q
[58] M. Hatanaka, H. Kandori, and A. Maeda, Localization and orientation of functional water molecules in bacteriorhodopsin as revealed by polarized Fourier transform infrared spectroscopy, Biophys. J. 73, 1001–1006 (1997),
https://doi.org/10.1016/S0006-3495(97)78133-5
[59] L.A. Curtiss, K. Raghavachari, P.C. Redfern, and J.A. Pople, Assessment of Gaussian-3 and density functional theories for a larger experimental test set, J. Chem. Phys. 112, 7374–7383 (2000),
https://doi.org/10.1063/1.481336
[60] M. Olivucci, T. Tran, G.A. Worth, and M.A. Robb, Unlocking the double bond in protonated Schiff bases by coherent superposition of S1 and S2, J. Phys. Chem. Lett. 12, 5639–5643 (2021),
https://doi.org/10.1021/acs.jpclett.1c01379
[61] T. Tran, G.A. Worth, and M.A. Robb, Control of nuclear dynamics in the benzene cation by electronic wavepacket composition, Commun. Chem. 4, 48 (2021),
https://doi.org/10.1038/s42004-021-00485-3
[62] H. Kandori, Y. Yamazaki, J. Sasaki, R. Needleman, J.K. Lanyi, and A. Maeda, Water-mediated proton transfer in proteins: An FTIR study of bacteriorhodopsin, J. Am. Chem. Soc. 117, 2118–2119 (1995),
https://doi.org/10.1021/ja00112a036
[63] R. Neutze, E. Pebay-Peyroula, K. Edman, A. Royant, J. Navarro, and E.M. Landau, Bacteriorhodopsin: a high-resolution structural view of vectorial proton transport, Biochim. Biophys. Acta Biomembr. 1565, 144–167 (2002),
https://doi.org/10.1016/S0005-2736(02)00566-7
[64] J.K. Lanyi and B. Schobert, Structural changes in the L photointermediate of bacteriorhodopsin, J. Mol. Biol. 365, 1379–1392 (2007),
https://doi.org/10.1016/j.jmb.2006.11.016
[65] E. Nango, A. Royant, M. Kubo, T. Nakane, C. Wickstrand, T. Kimura, T. Tanaka, K. Tono, C. Song, R. Tanaka, et al., A three-dimensional movie of structural changes in bacteriorhodopsin, Science 354, 1552–1557 (2016),
https://doi.org/10.2210/pdb5b6v/pdb
[66] P. Kietis, M. Vengris, and L. Valkunas, Electricalto-mechanical coupling in purple membranes: membrane as electrostrictive medium, Biophys. J. 80, 1631–1640 (2001),
https://doi.org/10.1016/S0006-3495(01)76135-8