Alternative ground states enable pathway switching in biological electron transfer
Abstract
Electron transfer is the simplest chemical reaction and constitutes the basis of a large variety of biological processes, such as photosynthesis and cellular respiration. Nature has evolved specific proteins and cofactors for these functions. The mechanisms optimizing biological electron transfer have been matter of intense debate, such as the role of the protein milieu between donor and acceptor sites. Here we propose a mechanism regulating long-range electron transfer in proteins. Specifically, we report a spectroscopic, electrochemical, and theoretical study on WT and single-mutant CuA redox centers from Thermus thermophilus, which shows that thermal fluctuations may populate two alternative ground-state electronic wave functions optimized for electron entry and exit, respectively, through two different and nearly perpendicular pathways. In conclusion, these findings suggest a unique role for alternative or “invisible” electronic ground states in directional electron transfer. Moreover, it is shown that this energy gap and, therefore, the equilibrium between ground states can be fine-tuned by minor perturbations, suggesting alternative ways through which protein–protein interactions and membrane potential may optimize and regulate electron–proton energy transduction.
- Authors:
-
- Univ. Nacional de Rosario, Rosario (Argentina)
- Univ. de Buenos Aires, Buenos Aires (Argentina)
- Oregon Health and Sciences Univ., Beaverton, OR (United States)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1132327
- Report Number(s):
- SLAC-REPRINT-2014-127
Journal ID: ISSN 0027-8424
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 109; Journal Issue: 43; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; cytochrome oxidase; invisible states; paramagnetic proteins; NMR; spectroscopy
Citation Formats
Abriata, Luciano A., Alvarez-Paggi, Damian, Ledesma, Gabirela N., Blackburn, Ninian J., Vila, Alejandro J., and Murgida, Daniel H. Alternative ground states enable pathway switching in biological electron transfer. United States: N. p., 2012.
Web. doi:10.1073/pnas.1204251109.
Abriata, Luciano A., Alvarez-Paggi, Damian, Ledesma, Gabirela N., Blackburn, Ninian J., Vila, Alejandro J., & Murgida, Daniel H. Alternative ground states enable pathway switching in biological electron transfer. United States. https://doi.org/10.1073/pnas.1204251109
Abriata, Luciano A., Alvarez-Paggi, Damian, Ledesma, Gabirela N., Blackburn, Ninian J., Vila, Alejandro J., and Murgida, Daniel H. Wed .
"Alternative ground states enable pathway switching in biological electron transfer". United States. https://doi.org/10.1073/pnas.1204251109. https://www.osti.gov/servlets/purl/1132327.
@article{osti_1132327,
title = {Alternative ground states enable pathway switching in biological electron transfer},
author = {Abriata, Luciano A. and Alvarez-Paggi, Damian and Ledesma, Gabirela N. and Blackburn, Ninian J. and Vila, Alejandro J. and Murgida, Daniel H.},
abstractNote = {Electron transfer is the simplest chemical reaction and constitutes the basis of a large variety of biological processes, such as photosynthesis and cellular respiration. Nature has evolved specific proteins and cofactors for these functions. The mechanisms optimizing biological electron transfer have been matter of intense debate, such as the role of the protein milieu between donor and acceptor sites. Here we propose a mechanism regulating long-range electron transfer in proteins. Specifically, we report a spectroscopic, electrochemical, and theoretical study on WT and single-mutant CuA redox centers from Thermus thermophilus, which shows that thermal fluctuations may populate two alternative ground-state electronic wave functions optimized for electron entry and exit, respectively, through two different and nearly perpendicular pathways. In conclusion, these findings suggest a unique role for alternative or “invisible” electronic ground states in directional electron transfer. Moreover, it is shown that this energy gap and, therefore, the equilibrium between ground states can be fine-tuned by minor perturbations, suggesting alternative ways through which protein–protein interactions and membrane potential may optimize and regulate electron–proton energy transduction.},
doi = {10.1073/pnas.1204251109},
url = {https://www.osti.gov/biblio/1132327},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 43,
volume = 109,
place = {United States},
year = {2012},
month = {10}
}
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Works referenced in this record:
Electron transfers in chemistry and biology
journal, August 1985
- Marcus, R. A.; Sutin, Norman
- Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics, Vol. 811, Issue 3
Nature of biological electron transfer
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Long-range electron transfer
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Electron Transfer Between Biological Molecules by Thermally Activated Tunneling
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- Proceedings of the National Academy of Sciences, Vol. 71, Issue 9
Mapping electron tunneling pathways: an algorithm that finds the "minimum length"/maximum coupling pathway between electron donors and acceptors in proteins
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- Betts, Jonathan N.; Beratan, David N.; Onuchic, Jose Nelson
- Journal of the American Chemical Society, Vol. 114, Issue 11
Protein dynamics and electron transfer: Electronic decoherence and non-Condon effects
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- Proceedings of the National Academy of Sciences, Vol. 102, Issue 10
Fluctuations in Biological and Bioinspired Electron-Transfer Reactions
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- Annual Review of Physical Chemistry, Vol. 61, Issue 1
Persistence of Structure Over Fluctuations in Biological Electron-Transfer Reactions
journal, October 2008
- Balabin, Ilya A.; Beratan, David N.; Skourtis, Spiros S.
- Physical Review Letters, Vol. 101, Issue 15
Protein electron transfer rates set by the bridging secondary and tertiary structure
journal, May 1991
- Beratan, D.; Betts, J.; Onuchic, J.
- Science, Vol. 252, Issue 5010
Ab Initio Based Calculations of Electron-Transfer Rates in Metalloproteins
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- Prytkova, Tatiana R.; Kurnikov, Igor V.; Beratan, David N.
- The Journal of Physical Chemistry B, Vol. 109, Issue 4
The currents of life: the terminal electron-transfer complex of respiration.
journal, December 1995
- Ramirez, B. E.; Malmstrom, B. G.; Winkler, J. R.
- Proceedings of the National Academy of Sciences, Vol. 92, Issue 26
Electron transfer among the Cu A -, heme b - and a 3 -centers of Thermus thermophilus cytochrome ba 3
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- Farver, Ole; Chen, Ying; Fee, James A.
- FEBS Letters, Vol. 580, Issue 14
The Electron Transfer Complex between Cytochrome c 552 and the Cu A Domain of the Thermus thermophilus ba 3 Oxidase : A COMBINED NMR AND COMPUTATIONAL APPROACH
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- Muresanu, Lucia; Pristovsek, Primoz; Löhr, Frank
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Internal Electron-Transfer Reactions in Cytochrome c Oxidase †
journal, January 1996
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- Biochemistry, Vol. 35, Issue 18
Electronic structure contributions to electron transfer in blue Cu and CuA
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- Randall, D. W.; Gamelin, D. R.; LaCroix, L. B.
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The Two-State Issue in the Mixed-Valence Binuclear Cu A Center in Cytochrome c Oxidase and N 2 O Reductase
journal, December 2006
- Gorelsky, Serge I.; Xie, Xiangjin; Chen, Ying
- Journal of the American Chemical Society, Vol. 128, Issue 51
Geometry, Reduction Potential, and Reorganization Energy of the Binuclear Cu A Site, Studied by Density Functional Theory
journal, August 2001
- Olsson, Mats H. M.; Ryde, Ulf
- Journal of the American Chemical Society, Vol. 123, Issue 32
Electronic Structure of the Ground and Excited States of the Cu A Site by NMR Spectroscopy
journal, February 2009
- Abriata, Luciano A.; Ledesma, Gabriela N.; Pierattelli, Roberta
- Journal of the American Chemical Society, Vol. 131, Issue 5
Understanding the Electronic Properties of the Cu A Site from the Soluble Domain of Cytochrome c Oxidase through Paramagnetic 1 H NMR †
journal, May 1998
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The Cu A Center of a Soluble Domain from Thermus Cytochrome ba 3 . An NMR Investigation of the Paramagnetic Protein
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The Met Axial Ligand Determines the Redox Potential in Cu A Sites
journal, October 2007
- Ledesma, Gabriela N.; Murgida, Daniel H.; Ly, Hoang Khoa
- Journal of the American Chemical Society, Vol. 129, Issue 39
Perturbations to the Geometric and Electronic Structure of the Cu A Site: Factors that Influence Delocalization and Their Contributions to Electron Transfer
journal, April 2008
- Xie, Xiangjin; Gorelsky, Serge I.; Sarangi, Ritimukta
- Journal of the American Chemical Society, Vol. 130, Issue 15
Spectroscopy of Mixed-Valence Cu A -Type Centers: Ligand-Field Control of Ground-State Properties Related to Electron Transfer
journal, June 1998
- Gamelin, Daniel R.; Randall, David W.; Hay, Michael T.
- Journal of the American Chemical Society, Vol. 120, Issue 21
Effect of Electron-Transfer Rate and Reorganization Energy on the Cyclic Voltammetric Response of Redox Adsorbates
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- Honeychurch, Michael J.
- Langmuir, Vol. 15, Issue 15
General expression of the linear potential sweep voltammogram in the case of diffusionless electrochemical systems
journal, July 1979
- Laviron, E.
- Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, Vol. 101, Issue 1
A Quantitative Description of the Ground-State Wave Function of Cu A by X-ray Absorption Spectroscopy: Comparison to Plastocyanin and Relevance to Electron Transfer
journal, June 2001
- DeBeer George, Serena; Metz, Markus; Szilagyi, Robert K.
- Journal of the American Chemical Society, Vol. 123, Issue 24
Heme-protein vibrational couplings in cytochrome c provide a dynamic link that connects the heme-iron and the protein surface
journal, May 2012
- Galinato, M. G. I.; Kleingardner, J. G.; Bowman, S. E. J.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 23
Interaction-induced Redox Switch in the Electron Transfer Complex Rusticyanin-Cytochrome c 4
journal, October 1999
- Giudici-Orticoni, Marie-Thérèse; Guerlesquin, Françoise; Bruschi, Mireille
- Journal of Biological Chemistry, Vol. 274, Issue 43
Transient binding of plastocyanin to its physiological redox partners modifies the copper site geometry
journal, October 2006
- Díaz-Moreno, Irene; Díaz-Quintana, Antonio; Díaz-Moreno, Sofía
- FEBS Letters, Vol. 580, Issue 26
Direct Observation of the Gating Step in Protein Electron Transfer: Electric-Field-Controlled Protein Dynamics
journal, July 2008
- Kranich, Anja; Ly, Hoang Khoa; Hildebrandt, Peter
- Journal of the American Chemical Society, Vol. 130, Issue 30
Molecular Basis of Coupled Protein and Electron Transfer Dynamics of Cytochrome c in Biomimetic Complexes
journal, April 2010
- Alvarez-Paggi, Damián; Martín, Diego F.; DeBiase, Pablo M.
- Journal of the American Chemical Society, Vol. 132, Issue 16
Probing Invisible, Low-Populated States of Protein Molecules by Relaxation Dispersion NMR Spectroscopy: An Application to Protein Folding
journal, March 2008
- Korzhnev, Dmitry M.; Kay, Lewis E.
- Accounts of Chemical Research, Vol. 41, Issue 3
New Tools Provide New Insights in NMR Studies of Protein Dynamics
journal, April 2006
- Mittermaier, A.
- Science, Vol. 312, Issue 5771
Systematic ab initio study of the electronic and magnetic properties of different pure and mixed iron systems
journal, May 2000
- Izquierdo, J.; Vega, A.; Balbás, L. C.
- Physical Review B, Vol. 61, Issue 20
A DFT-Based QM-MM Approach Designed for the Treatment of Large Molecular Systems: Application to Chorismate Mutase
journal, December 2003
- Crespo, Alejandro; Scherlis, Damián A.; Martí, Marcelo A.
- The Journal of Physical Chemistry B, Vol. 107, Issue 49
A novel cryoprotection scheme for enhancing the diffraction of crystals of recombinant cytochrome ba 3 oxidase from Thermus thermophilus
journal, February 2005
- Hunsicker-Wang, Laura M.; Pacoma, Ronald L.; Chen, Ying
- Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 3
Works referencing / citing this record:
The Cu A Center of a Soluble Domain from Thermus Cytochrome ba 3 . An NMR Investigation of the Paramagnetic Protein
journal, January 1996
- Bertini, Ivano; Bren, Kara L.; Clemente, Antonio
- Journal of the American Chemical Society, Vol. 118, Issue 46
General expression of the linear potential sweep voltammogram in the case of diffusionless electrochemical systems
journal, July 1979
- Laviron, E.
- Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, Vol. 101, Issue 1
Electronic Structure of the Ground and Excited States of the Cu A Site by NMR Spectroscopy
journal, February 2009
- Abriata, Luciano A.; Ledesma, Gabriela N.; Pierattelli, Roberta
- Journal of the American Chemical Society, Vol. 131, Issue 5
The Two-State Issue in the Mixed-Valence Binuclear Cu A Center in Cytochrome c Oxidase and N 2 O Reductase
journal, December 2006
- Gorelsky, Serge I.; Xie, Xiangjin; Chen, Ying
- Journal of the American Chemical Society, Vol. 128, Issue 51
A novel cryoprotection scheme for enhancing the diffraction of crystals of recombinant cytochrome ba 3 oxidase from Thermus thermophilus
journal, February 2005
- Hunsicker-Wang, Laura M.; Pacoma, Ronald L.; Chen, Ying
- Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 3
Long-range electron transfer
journal, February 2005
- Gray, H. B.; Winkler, J. R.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 10
Systematic ab initio study of the electronic and magnetic properties of different pure and mixed iron systems
journal, May 2000
- Izquierdo, J.; Vega, A.; Balbás, L. C.
- Physical Review B, Vol. 61, Issue 20
Understanding the Electronic Properties of the Cu A Site from the Soluble Domain of Cytochrome c Oxidase through Paramagnetic 1 H NMR †
journal, May 1998
- Salgado, Jesús; Warmerdam, Gertrüd; Bubacco, Luigi
- Biochemistry, Vol. 37, Issue 20
Protein dynamics and electron transfer: Electronic decoherence and non-Condon effects
journal, February 2005
- Skourtis, S. S.; Balabin, I. A.; Kawatsu, T.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 10
Heme-protein vibrational couplings in cytochrome c provide a dynamic link that connects the heme-iron and the protein surface
journal, May 2012
- Galinato, M. G. I.; Kleingardner, J. G.; Bowman, S. E. J.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 23
Persistence of Structure Over Fluctuations in Biological Electron-Transfer Reactions
journal, October 2008
- Balabin, Ilya A.; Beratan, David N.; Skourtis, Spiros S.
- Physical Review Letters, Vol. 101, Issue 15
Mapping electron tunneling pathways: an algorithm that finds the "minimum length"/maximum coupling pathway between electron donors and acceptors in proteins
journal, May 1992
- Betts, Jonathan N.; Beratan, David N.; Onuchic, Jose Nelson
- Journal of the American Chemical Society, Vol. 114, Issue 11
Interaction-induced Redox Switch in the Electron Transfer Complex Rusticyanin-Cytochrome c 4
journal, October 1999
- Giudici-Orticoni, Marie-Thérèse; Guerlesquin, Françoise; Bruschi, Mireille
- Journal of Biological Chemistry, Vol. 274, Issue 43
Transient binding of plastocyanin to its physiological redox partners modifies the copper site geometry
journal, October 2006
- Díaz-Moreno, Irene; Díaz-Quintana, Antonio; Díaz-Moreno, Sofía
- FEBS Letters, Vol. 580, Issue 26
Direct Observation of the Gating Step in Protein Electron Transfer: Electric-Field-Controlled Protein Dynamics
journal, July 2008
- Kranich, Anja; Ly, Hoang Khoa; Hildebrandt, Peter
- Journal of the American Chemical Society, Vol. 130, Issue 30
Probing Invisible, Low-Populated States of Protein Molecules by Relaxation Dispersion NMR Spectroscopy: An Application to Protein Folding
journal, March 2008
- Korzhnev, Dmitry M.; Kay, Lewis E.
- Accounts of Chemical Research, Vol. 41, Issue 3
Molecular Basis of Coupled Protein and Electron Transfer Dynamics of Cytochrome c in Biomimetic Complexes
journal, April 2010
- Alvarez-Paggi, Damián; Martín, Diego F.; DeBiase, Pablo M.
- Journal of the American Chemical Society, Vol. 132, Issue 16
Perturbations to the Geometric and Electronic Structure of the Cu A Site: Factors that Influence Delocalization and Their Contributions to Electron Transfer
journal, April 2008
- Xie, Xiangjin; Gorelsky, Serge I.; Sarangi, Ritimukta
- Journal of the American Chemical Society, Vol. 130, Issue 15
Internal Electron-Transfer Reactions in Cytochrome c Oxidase †
journal, January 1996
- Brzezinski, Peter
- Biochemistry, Vol. 35, Issue 18
Fluctuations in Biological and Bioinspired Electron-Transfer Reactions
journal, March 2010
- Skourtis, Spiros S.; Waldeck, David H.; Beratan, David N.
- Annual Review of Physical Chemistry, Vol. 61, Issue 1
Nature of biological electron transfer
journal, February 1992
- Moser, Christopher C.; Keske, Jonathan M.; Warncke, Kurt
- Nature, Vol. 355, Issue 6363
Ab Initio Based Calculations of Electron-Transfer Rates in Metalloproteins
journal, February 2005
- Prytkova, Tatiana R.; Kurnikov, Igor V.; Beratan, David N.
- The Journal of Physical Chemistry B, Vol. 109, Issue 4
A Quantitative Description of the Ground-State Wave Function of Cu A by X-ray Absorption Spectroscopy: Comparison to Plastocyanin and Relevance to Electron Transfer
journal, June 2001
- DeBeer George, Serena; Metz, Markus; Szilagyi, Robert K.
- Journal of the American Chemical Society, Vol. 123, Issue 24
Spectroscopy of Mixed-Valence Cu A -Type Centers: Ligand-Field Control of Ground-State Properties Related to Electron Transfer
journal, June 1998
- Gamelin, Daniel R.; Randall, David W.; Hay, Michael T.
- Journal of the American Chemical Society, Vol. 120, Issue 21
Electronic structure contributions to electron transfer in blue Cu and CuA
journal, February 2000
- Randall, D. W.; Gamelin, D. R.; LaCroix, L. B.
- JBIC Journal of Biological Inorganic Chemistry, Vol. 5, Issue 1
Effect of Electron-Transfer Rate and Reorganization Energy on the Cyclic Voltammetric Response of Redox Adsorbates
journal, July 1999
- Honeychurch, Michael J.
- Langmuir, Vol. 15, Issue 15
Electron Transfer Between Biological Molecules by Thermally Activated Tunneling
journal, September 1974
- Hopfield, J. J.
- Proceedings of the National Academy of Sciences, Vol. 71, Issue 9
Electron transfers in chemistry and biology
journal, August 1985
- Marcus, R. A.; Sutin, Norman
- Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics, Vol. 811, Issue 3
Geometry, Reduction Potential, and Reorganization Energy of the Binuclear Cu A Site, Studied by Density Functional Theory
journal, August 2001
- Olsson, Mats H. M.; Ryde, Ulf
- Journal of the American Chemical Society, Vol. 123, Issue 32
Protein electron transfer rates set by the bridging secondary and tertiary structure
journal, May 1991
- Beratan, D.; Betts, J.; Onuchic, J.
- Science, Vol. 252, Issue 5010
A DFT-Based QM-MM Approach Designed for the Treatment of Large Molecular Systems: Application to Chorismate Mutase
journal, December 2003
- Crespo, Alejandro; Scherlis, Damián A.; Martí, Marcelo A.
- The Journal of Physical Chemistry B, Vol. 107, Issue 49
The currents of life: the terminal electron-transfer complex of respiration.
journal, December 1995
- Ramirez, B. E.; Malmstrom, B. G.; Winkler, J. R.
- Proceedings of the National Academy of Sciences, Vol. 92, Issue 26
The Met Axial Ligand Determines the Redox Potential in Cu A Sites
journal, October 2007
- Ledesma, Gabriela N.; Murgida, Daniel H.; Ly, Hoang Khoa
- Journal of the American Chemical Society, Vol. 129, Issue 39
Electron transfer among the Cu A -, heme b - and a 3 -centers of Thermus thermophilus cytochrome ba 3
journal, May 2006
- Farver, Ole; Chen, Ying; Fee, James A.
- FEBS Letters, Vol. 580, Issue 14
The Electron Transfer Complex between Cytochrome c 552 and the Cu A Domain of the Thermus thermophilus ba 3 Oxidase : A COMBINED NMR AND COMPUTATIONAL APPROACH
journal, March 2006
- Muresanu, Lucia; Pristovsek, Primoz; Löhr, Frank
- Journal of Biological Chemistry, Vol. 281, Issue 20
New Tools Provide New Insights in NMR Studies of Protein Dynamics
journal, April 2006
- Mittermaier, A.
- Science, Vol. 312, Issue 5771