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Title: 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:
 [1];  [2];  [1];  [3];  [1];  [2]
  1. Univ. Nacional de Rosario, Rosario (Argentina)
  2. Univ. de Buenos Aires, Buenos Aires (Argentina)
  3. 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:
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. doi: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. doi: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},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 43,
volume = 109,
place = {United States},
year = {2012},
month = {10}
}

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Free Publicly Available Full Text
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Cited by: 17 works
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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
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Nature of biological electron transfer
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Long-range electron transfer
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  • DOI: 10.1073/pnas.0408029102

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
  • DOI: 10.1073/pnas.71.9.3640

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
  • DOI: 10.1021/ja00037a004

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
  • DOI: 10.1073/pnas.0409047102

Fluctuations in Biological and Bioinspired Electron-Transfer Reactions
journal, March 2010


Persistence of Structure Over Fluctuations in Biological Electron-Transfer Reactions
journal, October 2008


Protein electron transfer rates set by the bridging secondary and tertiary structure
journal, May 1991


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
  • DOI: 10.1021/jp0457491

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
  • DOI: 10.1073/pnas.92.26.11949

Electron transfer among the Cu A -, heme b - and a 3 -centers of Thermus thermophilus cytochrome ba 3
journal, May 2006


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
  • DOI: 10.1074/jbc.M601108200

Internal Electron-Transfer Reactions in Cytochrome c Oxidase
journal, January 1996


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
  • DOI: 10.1007/s007750050003

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
  • DOI: 10.1021/ja067583i

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
  • DOI: 10.1021/ja010315u

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
  • DOI: 10.1021/ja8079669

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
  • DOI: 10.1021/bi9728598

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
  • DOI: 10.1021/ja9621410

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
  • DOI: 10.1021/ja0731221

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
  • DOI: 10.1021/ja7102668

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
  • DOI: 10.1021/ja973161k

General expression of the linear potential sweep voltammogram in the case of diffusionless electrochemical systems
journal, July 1979


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
  • DOI: 10.1021/ja004109i

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
  • DOI: 10.1073/pnas.1200345109

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
  • DOI: 10.1074/jbc.274.43.30365

Transient binding of plastocyanin to its physiological redox partners modifies the copper site geometry
journal, October 2006


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
  • DOI: 10.1021/ja8016895

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
  • DOI: 10.1021/ja910707r

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
  • DOI: 10.1021/ar700189y

New Tools Provide New Insights in NMR Studies of Protein Dynamics
journal, April 2006


Systematic ab initio study of the electronic and magnetic properties of different pure and mixed iron systems
journal, May 2000


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
  • DOI: 10.1021/jp036236h

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
  • DOI: 10.1107/S0907444904033906

    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
    • DOI: 10.1021/ja9621410

    General expression of the linear potential sweep voltammogram in the case of diffusionless electrochemical systems
    journal, July 1979


    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
    • DOI: 10.1021/ja8079669

    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
    • DOI: 10.1021/ja067583i

    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
    • DOI: 10.1107/s0907444904033906

    Long-range electron transfer
    journal, February 2005

    • Gray, H. B.; Winkler, J. R.
    • Proceedings of the National Academy of Sciences, Vol. 102, Issue 10
    • DOI: 10.1073/pnas.0408029102

    Systematic ab initio study of the electronic and magnetic properties of different pure and mixed iron systems
    journal, May 2000


    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
    • DOI: 10.1021/bi9728598

    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
    • DOI: 10.1073/pnas.0409047102

    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
    • DOI: 10.1073/pnas.1200345109

    Persistence of Structure Over Fluctuations in Biological Electron-Transfer Reactions
    journal, October 2008


    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
    • DOI: 10.1021/ja00037a004

    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
    • DOI: 10.1074/jbc.274.43.30365

    Transient binding of plastocyanin to its physiological redox partners modifies the copper site geometry
    journal, October 2006


    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
    • DOI: 10.1021/ja8016895

    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
    • DOI: 10.1021/ar700189y

    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
    • DOI: 10.1021/ja910707r

    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
    • DOI: 10.1021/ja7102668

    Internal Electron-Transfer Reactions in Cytochrome c Oxidase
    journal, January 1996


    Fluctuations in Biological and Bioinspired Electron-Transfer Reactions
    journal, March 2010


    Nature of biological electron transfer
    journal, February 1992

    • Moser, Christopher C.; Keske, Jonathan M.; Warncke, Kurt
    • Nature, Vol. 355, Issue 6363
    • DOI: 10.1038/355796a0

    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
    • DOI: 10.1021/jp0457491

    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
    • DOI: 10.1021/ja004109i

    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
    • DOI: 10.1021/ja973161k

    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
    • DOI: 10.1007/s007750050003

    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
    • DOI: 10.1073/pnas.71.9.3640

    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
    • DOI: 10.1016/0304-4173(85)90014-x

    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
    • DOI: 10.1021/ja010315u

    Protein electron transfer rates set by the bridging secondary and tertiary structure
    journal, May 1991


    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
    • DOI: 10.1021/jp036236h

    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
    • DOI: 10.1073/pnas.92.26.11949

    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
    • DOI: 10.1021/ja0731221

    Electron transfer among the Cu A -, heme b - and a 3 -centers of Thermus thermophilus cytochrome ba 3
    journal, May 2006


    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
    • DOI: 10.1074/jbc.m601108200

    New Tools Provide New Insights in NMR Studies of Protein Dynamics
    journal, April 2006