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Title: Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins

Abstract

Channel and pump rhodopsins use energy from light absorbed by a covalently bound retinal chromophore to transport ions across membranes of microbial cells. Ion transfer steps, including proton transfer, can couple to changes in protein conformational dynamics and water positions. Although general principles of how microbial rhodopsins function are largely understood, key issues pertaining to reaction mechanisms remain unclear. Here, we compare the protonation-coupled dynamics of pump and channelrhodopsins, highlighting the roles that water dynamics, protein electrostatics and protein flexibility can have in ion transport mechanisms. We discuss observations supporting important functional roles of inter- and intra-helical carboxylate/hydroxyl hydrogen-bonding motifs. Specifically, we use the proton pump bacteriorhodopsin, the sodium pump KR2, channelrhodopsins and Anabaena sensory rhodopsin. We outline the usefulness of theoretic biophysics approaches to the study of retinal proteins, challenges in studying the hydrogen-bond dynamics of rhodopsin active sites, and implications for conformational coupling in membrane transporters.

Authors:
 [1]; ORCiD logo [2]
  1. Freie Univ., Berlin (Germany). Dept. of Physics
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Molecular Biophysics; Univ. of Tennessee, Knoxville, TN (United States). Dept. of Biochemistry, Cellular and Molecular Biology
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1394768
Grant/Contract Number:  
AC05-00OR22725; SFB 1078; bec00063
Resource Type:
Accepted Manuscript
Journal Name:
Photochemistry and Photobiology
Additional Journal Information:
Journal Volume: 93; Journal Issue: 6; Journal ID: ISSN 0031-8655
Publisher:
The American Society of Photobiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Bondar, Ana-Nicoleta, and Smith, Jeremy C. Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins. United States: N. p., 2017. Web. doi:10.1111/php.12790.
Bondar, Ana-Nicoleta, & Smith, Jeremy C. Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins. United States. doi:10.1111/php.12790.
Bondar, Ana-Nicoleta, and Smith, Jeremy C. Tue . "Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins". United States. doi:10.1111/php.12790. https://www.osti.gov/servlets/purl/1394768.
@article{osti_1394768,
title = {Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins},
author = {Bondar, Ana-Nicoleta and Smith, Jeremy C.},
abstractNote = {Channel and pump rhodopsins use energy from light absorbed by a covalently bound retinal chromophore to transport ions across membranes of microbial cells. Ion transfer steps, including proton transfer, can couple to changes in protein conformational dynamics and water positions. Although general principles of how microbial rhodopsins function are largely understood, key issues pertaining to reaction mechanisms remain unclear. Here, we compare the protonation-coupled dynamics of pump and channelrhodopsins, highlighting the roles that water dynamics, protein electrostatics and protein flexibility can have in ion transport mechanisms. We discuss observations supporting important functional roles of inter- and intra-helical carboxylate/hydroxyl hydrogen-bonding motifs. Specifically, we use the proton pump bacteriorhodopsin, the sodium pump KR2, channelrhodopsins and Anabaena sensory rhodopsin. We outline the usefulness of theoretic biophysics approaches to the study of retinal proteins, challenges in studying the hydrogen-bond dynamics of rhodopsin active sites, and implications for conformational coupling in membrane transporters.},
doi = {10.1111/php.12790},
journal = {Photochemistry and Photobiology},
number = 6,
volume = 93,
place = {United States},
year = {2017},
month = {7}
}

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Works referenced in this record:

Structural alterations for proton translocation in the M state of wild-type bacteriorhodopsin
journal, August 2000

  • Sass, Hans Jürgen; Büldt, Georg; Gessenich, Ralf
  • Nature, Vol. 406, Issue 6796
  • DOI: 10.1038/35020607

Bacteriorhodopsin: Would the real structural intermediates please stand up?
journal, March 2015

  • Wickstrand, Cecilia; Dods, Robert; Royant, Antoine
  • Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1850, Issue 3
  • DOI: 10.1016/j.bbagen.2014.05.021

Key Role of Active-Site Water Molecules in Bacteriorhodopsin Proton-Transfer Reactions
journal, November 2008

  • Bondar, Ana-Nicoleta; Baudry, Jerome; Suhai, Sándor
  • The Journal of Physical Chemistry B, Vol. 112, Issue 47
  • DOI: 10.1021/jp801916f

Deformation of Helix C in the Low Temperature L-intermediate of Bacteriorhodopsin
journal, October 2003

  • Edman, Karl; Royant, Antoine; Larsson, Gisela
  • Journal of Biological Chemistry, Vol. 279, Issue 3
  • DOI: 10.1074/jbc.M300709200

Temporal evolution of helix hydration in a light-gated ion channel correlates with ion conductance
journal, October 2015

  • Lórenz-Fonfría, Víctor A.; Bamann, Christian; Resler, Tom
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 43
  • DOI: 10.1073/pnas.1511462112

Functional interactions in bacteriorhodopsin: a theoretical analysis of retinal hydrogen bonding with water
journal, January 1995


Structure of bacteriorhodopsin at 1.55 Å resolution
journal, August 1999

  • Luecke, Hartmut; Schobert, Brigitte; Richter, Hans-Thomas
  • Journal of Molecular Biology, Vol. 291, Issue 4
  • DOI: 10.1006/jmbi.1999.3027

Structural Changes in the L Photointermediate of Bacteriorhodopsin
journal, February 2007


Dynamics of the Plasma Membrane Proton Pump
journal, October 2014


An approach to computing electrostatic charges for molecules
journal, April 1984

  • Singh, U. Chandra; Kollman, Peter A.
  • Journal of Computational Chemistry, Vol. 5, Issue 2
  • DOI: 10.1002/jcc.540050204

Ab initio quantum chemical analysis of Schiff base-water interactions in bacteriorhodopsin
journal, October 1993


Key Role of Electrostatic Interactions in Bacteriorhodopsin Proton Transfer
journal, November 2004

  • Bondar, Ana-Nicoleta; Fischer, Stefan; Smith, Jeremy C.
  • Journal of the American Chemical Society, Vol. 126, Issue 44
  • DOI: 10.1021/ja047982i

Channelrhodopsins: A bioinformatics perspective
journal, May 2014

  • del Val, Coral; Royuela-Flor, José; Milenkovic, Stefan
  • Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1837, Issue 5
  • DOI: 10.1016/j.bbabio.2013.11.005

Thr 94 and Wat2b Effect Protonation of the Retinal Chromophore in Rhodopsin
journal, July 2003

  • Buss, Volker; Sugihara, Minoru; Entel, Peter
  • Angewandte Chemie International Edition, Vol. 42, Issue 28
  • DOI: 10.1002/anie.200351034

Charge stabilization mechanism in the visual and purple membrane pigments.
journal, June 1978


Alternative translocation of protons and halide ions by bacteriorhodopsin.
journal, June 1991

  • Der, A.; Szaraz, S.; Toth-Boconadi, R.
  • Proceedings of the National Academy of Sciences, Vol. 88, Issue 11
  • DOI: 10.1073/pnas.88.11.4751

Ser/Thr Motifs in Transmembrane Proteins: Conservation Patterns and Effects on Local Protein Structure and Dynamics
journal, July 2012

  • del Val, Coral; White, Stephen H.; Bondar, Ana-Nicoleta
  • The Journal of Membrane Biology, Vol. 245, Issue 11
  • DOI: 10.1007/s00232-012-9452-4

The Retinal Conformation and its Environment in Rhodopsin in Light of a New 2.2Å Crystal Structure
journal, September 2004

  • Okada, Tetsuji; Sugihara, Minoru; Bondar, Ana-Nicoleta
  • Journal of Molecular Biology, Vol. 342, Issue 2
  • DOI: 10.1016/j.jmb.2004.07.044

Halorhodopsin pumps Cl and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions
journal, October 2014

  • Song, Yifan; Gunner, M. R.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 46
  • DOI: 10.1073/pnas.1411119111

Mechanism by which Untwisting of Retinal Leads to Productive Bacteriorhodopsin Photocycle States
journal, August 2014

  • Wolter, Tino; Elstner, Marcus; Fischer, Stefan
  • The Journal of Physical Chemistry B, Vol. 119, Issue 6
  • DOI: 10.1021/jp505818r

Dynamics of SecY Translocons with Translocation-Defective Mutations
journal, July 2010


Hydrogen bond dynamics in membrane protein function
journal, April 2012

  • Bondar, Ana-Nicoleta; White, Stephen H.
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1818, Issue 4
  • DOI: 10.1016/j.bbamem.2011.11.035

Engineering an Inward Proton Transport from a Bacterial Sensor Rhodopsin
journal, November 2009

  • Kawanabe, Akira; Furutani, Yuji; Jung, Kwang-Hwan
  • Journal of the American Chemical Society, Vol. 131, Issue 45
  • DOI: 10.1021/ja904855g

Can coordinate driving describe proton transfer coupled to complex protein motions?
journal, January 2004


CHARMM: The biomolecular simulation program
journal, July 2009

  • Brooks, B. R.; Brooks, C. L.; Mackerell, A. D.
  • Journal of Computational Chemistry, Vol. 30, Issue 10
  • DOI: 10.1002/jcc.21287

Suppression of the back proton-transfer from Asp85 to the retinal Schiff base in bacteriorhodopsin: A theoretical analysis of structural elements
journal, March 2007

  • Bondar, Ana-Nicoleta; Suhai, Sándor; Fischer, Stefan
  • Journal of Structural Biology, Vol. 157, Issue 3
  • DOI: 10.1016/j.jsb.2006.10.007

Crystallographic Structure of the K Intermediate of Bacteriorhodopsin: Conservation of Free Energy after Photoisomerization of the Retinal
journal, August 2002


Mechanism of a proton pump analyzed with computer simulations
journal, April 2009

  • Bondar, Ana-Nicoleta; Smith, Jeremy C.; Elstner, Marcus
  • Theoretical Chemistry Accounts, Vol. 125, Issue 3-6
  • DOI: 10.1007/s00214-009-0565-5

Amino acid preferences for specific locations at the ends of alpha helices
journal, June 1988


Crystal Structure of the L Intermediate of Bacteriorhodopsin: Evidence for Vertical Translocation of a Water Molecule during the Proton Pumping Cycle
journal, January 2004

  • Kouyama, Tsutomu; Nishikawa, Taichi; Tokuhisa, Takeshi
  • Journal of Molecular Biology, Vol. 335, Issue 2
  • DOI: 10.1016/j.jmb.2003.10.068

Structure of an Inward Proton-Transporting Anabaena Sensory Rhodopsin Mutant: Mechanistic Insights
journal, September 2016

  • Dong, Bamboo; Sánchez-Magraner, Lissete; Luecke, Hartmut
  • Biophysical Journal, Vol. 111, Issue 5
  • DOI: 10.1016/j.bpj.2016.04.055

Coupling between inter-helical hydrogen bonding and water dynamics in a proton transporter
journal, April 2014

  • del Val, Coral; Bondar, Luiza; Bondar, Ana-Nicoleta
  • Journal of Structural Biology, Vol. 186, Issue 1
  • DOI: 10.1016/j.jsb.2014.02.010

QM/MM investigation of the hydrogen-bonding interactions in putative K and early-M intermediates of the bacteriorhodopsin photocycle
journal, September 2005


Proton Transfer in Bacteriorhodopsin:  Structure, Excitation, IR Spectra, and Potential Energy Surface Analyses by an ab Initio QM/MM Method
journal, November 2000

  • Hayashi, Shigehiko; Ohmine, Iwao
  • The Journal of Physical Chemistry B, Vol. 104, Issue 45
  • DOI: 10.1021/jp001508r

Helix signals in proteins
journal, June 1988


Proton-Coupled Dynamics in Lactose Permease
journal, November 2012


Crystal structure of the channelrhodopsin light-gated cation channel
journal, January 2012

  • Kato, Hideaki E.; Zhang, Feng; Yizhar, Ofer
  • Nature, Vol. 482, Issue 7385
  • DOI: 10.1038/nature10870

Anabaena Sensory Rhodopsin: A Photochromic Color Sensor at 2.0 A
journal, November 2004


A combined quantum mechanical and molecular mechanical potential for molecular dynamics simulations
journal, July 1990

  • Field, Martin J.; Bash, Paul A.; Karplus, Martin
  • Journal of Computational Chemistry, Vol. 11, Issue 6
  • DOI: 10.1002/jcc.540110605

CHARMM: A program for macromolecular energy, minimization, and dynamics calculations
journal, July 1983

  • Brooks, Bernard R.; Bruccoleri, Robert E.; Olafson, Barry D.
  • Journal of Computational Chemistry, Vol. 4, Issue 2
  • DOI: 10.1002/jcc.540040211

Three-dimensional model of purple membrane obtained by electron microscopy
journal, September 1975

  • Henderson, R.; Unwin, P. N. T.
  • Nature, Vol. 257, Issue 5521
  • DOI: 10.1038/257028a0

Structural and energetic determinants of primary proton transfer in bacteriorhodopsin
journal, January 2006

  • Bondar, Ana-Nicoleta; Smith, Jeremy C.; Fischer, Stefan
  • Photochem. Photobiol. Sci., Vol. 5, Issue 6
  • DOI: 10.1039/B516451F

Ground-state properties of the retinal molecule: from quantum mechanical to classical mechanical computations of retinal proteins
journal, October 2011

  • Bondar, Ana-Nicoleta; Knapp-Mohammady, Michaela; Suhai, Sándor
  • Theoretical Chemistry Accounts, Vol. 130, Issue 4-6
  • DOI: 10.1007/s00214-011-1054-1

Protein, lipid and water organization in bacteriorhodopsin crystals: a molecular view of the purple membrane at 1.9 Å resolution
journal, August 1999


Coupling of charge stabilization, torsion and bond alternation in light-induced reactions of visual pigments
journal, May 1978


Control of the Pump Cycle in Bacteriorhodopsin: Mechanisms Elucidated by Solid-State NMR of the D85N Mutant
journal, February 2002


Tuning of Retinal Twisting in Bacteriorhodopsin Controls the Directionality of the Early Photocycle Steps
journal, August 2005

  • Bondar, Ana-Nicoleta; Fischer, Stefan; Suhai, Sándor
  • The Journal of Physical Chemistry B, Vol. 109, Issue 31
  • DOI: 10.1021/jp0531255

Specific Damage Induced by X-ray Radiation and Structural Changes in the Primary Photoreaction of Bacteriorhodopsin
journal, November 2002


Mechanism of Primary Proton Transfer in Bacteriorhodopsin
journal, July 2004


Altered Hydrogen Bonding of Arg82 during the Proton Pump Cycle of Bacteriorhodopsin:  A Low-Temperature Polarized FTIR Spectroscopic Study
journal, July 2004

  • Tanimoto, Taro; Shibata, Mikihiro; Belenky, Marina
  • Biochemistry, Vol. 43, Issue 29
  • DOI: 10.1021/bi049368p

Early Formation of the Ion-Conducting Pore in Channelrhodopsin-2
journal, December 2014

  • Kuhne, Jens; Eisenhauer, Kirstin; Ritter, Eglof
  • Angewandte Chemie International Edition, Vol. 54, Issue 16
  • DOI: 10.1002/anie.201410180

A three-dimensional movie of structural changes in bacteriorhodopsin
journal, December 2016

  • Nango, Eriko; Royant, Antoine; Kubo, Minoru
  • Science, Vol. 354, Issue 6319, p. 1552-1557
  • DOI: 10.1126/science.aah3497

Structural basis for Na+ transport mechanism by a light-driven Na+ pump
journal, April 2015

  • Kato, Hideaki E.; Inoue, Keiichi; Abe-Yoshizumi, Rei
  • Nature, Vol. 521, Issue 7550
  • DOI: 10.1038/nature14322

High-resolution X-ray structure of an early intermediate in the bacteriorhodopsin photocycle
journal, October 1999

  • Edman, Karl; Nollert, Peter; Royant, Antoine
  • Nature, Vol. 401, Issue 6755
  • DOI: 10.1038/44623

Proton Transport by Halorhodopsin
journal, January 1996

  • Váró, György; Brown, Leonid S.; Needleman, Richard
  • Biochemistry, Vol. 35, Issue 21
  • DOI: 10.1021/bi9601159

Conversion of bacteriorhodopsin into a chloride ion pump
journal, July 1995


Water Rearrangement around the Schiff Base in the Late K (K L ) Intermediate of the Bacteriorhodopsin Photocycle
journal, January 2004

  • Maeda, Akio; Verhoeven, Michiel A.; Lugtenburg, Johan
  • The Journal of Physical Chemistry B, Vol. 108, Issue 3
  • DOI: 10.1021/jp030484w

Transient protonation changes in channelrhodopsin-2 and their relevance to channel gating
journal, March 2013

  • Lorenz-Fonfria, V. A.; Resler, T.; Krause, N.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 14
  • DOI: 10.1073/pnas.1219502110

Accessing protein conformational ensembles using room-temperature X-ray crystallography
journal, September 2011

  • Fraser, J. S.; van den Bedem, H.; Samelson, A. J.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 39
  • DOI: 10.1073/pnas.1111325108

Conversion of Channelrhodopsin into a Light-Gated Chloride Channel
journal, March 2014


Coupling of Retinal, Protein, and Water Dynamics in Squid Rhodopsin
journal, October 2010

  • Jardón-Valadez, Eduardo; Bondar, Ana-Nicoleta; Tobias, Douglas J.
  • Biophysical Journal, Vol. 99, Issue 7
  • DOI: 10.1016/j.bpj.2010.06.067

Polarization Effects Stabilize Bacteriorhodopsin’s Chromophore Binding Pocket: A Molecular Dynamics Study
journal, July 2009

  • Babitzki, G.; Denschlag, R.; Tavan, P.
  • The Journal of Physical Chemistry B, Vol. 113, Issue 30
  • DOI: 10.1021/jp902428x

Crystal structure of metarhodopsin II
journal, March 2011

  • Choe, Hui-Woog; Kim, Yong Ju; Park, Jung Hee
  • Nature, Vol. 471, Issue 7340
  • DOI: 10.1038/nature09789

VMD: Visual molecular dynamics
journal, February 1996