Structural insights into functional properties of the oxidized form of cytochrome c oxidase

Ishigami, Izumi; Sierra, Raymond G.; Su, Zhen; Peck, Ariana; Wang, Cong; Poitevin, Frederic; Lisova, Stella; Hayes, Brandon; Moss, III, Frank R.; Boutet, Sébastien; Sublett, Robert E.; Yoon, Chun Hong; Yeh, Syun-Ru; Rousseau, Denis L.

doi:10.1038/s41467-023-41533-x

Title: Structural insights into functional properties of the oxidized form of cytochrome c oxidase

Journal Article · 16 September 2023 · Nature Communications

DOI: https://doi.org/10.1038/s41467-023-41533-x · OSTI ID:2000580

;

; Su, Zhen; Peck, Ariana; Wang, Cong; Poitevin, Frederic; Lisova, Stella; Hayes, Brandon; Moss, III, Frank R.;

; Sublett, Robert E.;

;

Abstract Cytochrome c oxidase (C c O) is an essential enzyme in mitochondrial and bacterial respiration. It catalyzes the four-electron reduction of molecular oxygen to water and harnesses the chemical energy to translocate four protons across biological membranes. The turnover of the C c O reaction involves an oxidative phase, in which the reduced enzyme (R) is oxidized to the metastable O _H state, and a reductive phase, in which O _H is reduced back to the R state. During each phase, two protons are translocated across the membrane. However, if O _H is allowed to relax to the resting oxidized state (O), a redox equivalent to O _H , its subsequent reduction to R is incapable of driving proton translocation. Here, with resonance Raman spectroscopy and serial femtosecond X-ray crystallography (SFX), we show that the heme a ₃ iron and Cu _B in the active site of the O state, like those in the O _H state, are coordinated by a hydroxide ion and a water molecule, respectively. However, Y244, critical for the oxygen reduction chemistry, is in the neutral protonated form, which distinguishes O from O _H , where Y244 is in the deprotonated tyrosinate form. These structural characteristics of O provide insights into the proton translocation mechanism of C c O.

View Journal Article

Cite

Export

Save

Sponsoring Organization:: USDOE

Grant/Contract Number:: NONE; AC02-76SF00515

OSTI ID:: 2000580

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 14; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (71)

A Protonated Water Cluster as a Transient Proton-Loading Site in Cytochrome c Oxidase Supekar, Shreyas; Gamiz-Hernandez, Ana P.; Kaila, Ville R. I. Angewandte Chemie International Edition, Vol. 55, Issue 39 https://doi.org/10.1002/anie.201603606	journal	August 2016
A chemically explicit model for the mechanism of proton pumping in heme–copper oxidases Sharpe, Martyn A.; Ferguson-Miller, Shelagh Journal of Bioenergetics and Biomembranes, Vol. 40, Issue 5 https://doi.org/10.1007/s10863-008-9182-6	journal	October 2008
Proton uptake by cytochrome c oxidase on reduction and on ligand binding Mitchell, Roy; Rich, Peter R. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1186, Issue 1-2 https://doi.org/10.1016/0005-2728(94)90130-9	journal	June 1994
Coupling of charge and proton movement in cytochrome c oxidase Rich, Peter R.; Meunier, Brigitte; Mitchell, Roy Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1275, Issue 1-2 https://doi.org/10.1016/0005-2728(96)00055-2	journal	July 1996
The role of the D- and K-pathways of proton transfer in the function of the haem–copper oxidases Wikström, Mårten; Jasaitis, Audrius; Backgren, Camilla Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1459, Issue 2-3 https://doi.org/10.1016/S0005-2728(00)00191-2	journal	August 2000
Evidence for a Hydroxide Intermediate in Cytochrome c Oxidase Han, S. W.; Ching, Y. C.; Rousseau, D. L. Journal of Biological Chemistry, Vol. 264, Issue 12 https://doi.org/10.1016/S0021-9258(18)83469-X	journal	April 1989
An infrared study of CO binding to heart cytochrome c oxidase and hemoglobin A. Implications re O2 reactions. Yoshikawa, S.; Choc, M. G.; O'Toole, M. C. Journal of Biological Chemistry, Vol. 252, Issue 15 https://doi.org/10.1016/S0021-9258(19)63379-X	journal	August 1977
The reaction of cytochrome oxidase with cyanide. Preparation of the rapidly reacting form and its conversion to the slowly reacting form. Baker, G. M.; Noguchi, M.; Palmer, G. Journal of Biological Chemistry, Vol. 262, Issue 2 https://doi.org/10.1016/S0021-9258(19)75825-6	journal	January 1987
High resolution crystal structure of Paracoccus denitrificans cytochrome c oxidase: New insights into the active site and the proton transfer pathways Koepke, Juergen; Olkhova, Elena; Angerer, Heike Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1787, Issue 6 https://doi.org/10.1016/j.bbabio.2009.04.003	journal	June 2009
The identity of the transient proton loading site of the proton-pumping mechanism of cytochrome c oxidase Kaila, Ville R. I.; Sharma, Vivek; Wikström, Mårten Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1807, Issue 1 https://doi.org/10.1016/j.bbabio.2010.08.014	journal	January 2011
A combined quantum chemical and crystallographic study on the oxidized binuclear center of cytochrome c oxidase Kaila, Ville R. I.; Oksanen, Esko; Goldman, Adrian Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1807, Issue 7 https://doi.org/10.1016/j.bbabio.2010.12.016	journal	July 2011
Lysine 362 in cytochrome c oxidase regulates opening of the K-channel via changes in p K A and conformation Woelke, Anna Lena; Galstyan, Gegham; Knapp, Ernst-Walter Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1837, Issue 12 https://doi.org/10.1016/j.bbabio.2014.08.003	journal	December 2014
The role of the K-channel and the active-site tyrosine in the catalytic mechanism of cytochrome c oxidase Sharma, Vivek; Wikström, Mårten Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1857, Issue 8 https://doi.org/10.1016/j.bbabio.2016.02.008	journal	August 2016
Structures of the intermediates in the catalytic cycle of mitochondrial cytochrome c oxidase Wikström, Mårten; Gennis, Robert B.; Rich, Peter R. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1864, Issue 2 https://doi.org/10.1016/j.bbabio.2022.148933	journal	April 2023
Critical roles of the CuB site in efficient proton pumping as revealed by crystal structures of mammalian cytochrome c oxidase catalytic intermediates Shimada, Atsuhiro; Hara, Fumiyoshi; Shinzawa-Itoh, Kyoko Journal of Biological Chemistry, Vol. 297, Issue 3 https://doi.org/10.1016/j.jbc.2021.100967	journal	September 2021
Temperature-dependent structural transition following X-ray-induced metal center reduction in oxidized cytochrome c oxidase Ishigami, Izumi; Russi, Silvia; Cohen, Aina Journal of Biological Chemistry, Vol. 298, Issue 4 https://doi.org/10.1016/j.jbc.2022.101799	journal	April 2022
Redox-driven membrane-bound proton pumps Brzezinski, Peter Trends in Biochemical Sciences, Vol. 29, Issue 7 https://doi.org/10.1016/j.tibs.2004.05.008	journal	July 2004
Mechanism of Oxygen Reduction in Cytochrome c Oxidase and the Role of the Active Site Tyrosine Blomberg, Margareta R. A. Biochemistry, Vol. 55, Issue 3 https://doi.org/10.1021/acs.biochem.5b01205	journal	January 2016
Oxygen Activation and Energy Conservation by Cytochrome c Oxidase Wikström, Mårten; Krab, Klaas; Sharma, Vivek Chemical Reviews, Vol. 118, Issue 5 https://doi.org/10.1021/acs.chemrev.7b00664	journal	January 2018
Spin State and Axial Ligand Bonding in the Hydroxide Complexes of Metmyoglobin, Methemoglobin, and Horseradish Peroxidase at Room and Low Temperatures Feis, Alessandro; Marzocchi, Mario P.; Paoli, Mauro Biochemistry, Vol. 33, Issue 15 https://doi.org/10.1021/bi00181a019	journal	April 1994
Reactions of nitric oxide with cytochrome c oxidase Brudvig, Gary W.; Stevens, Tom H.; Chan, Sunney I. Biochemistry, Vol. 19, Issue 23 https://doi.org/10.1021/bi00564a020	journal	November 1980
Synchrotron X-ray-Induced Photoreduction of Ferric Myoglobin Nitrite Crystals Gives the Ferrous Derivative with Retention of the O-Bonded Nitrite Ligand Yi, Jun; Orville, Allen M.; Skinner, John M. Biochemistry, Vol. 49, Issue 29 https://doi.org/10.1021/bi100801g	journal	July 2010
Time-Resolved Resonance Raman Evidence for Tight Coupling between Electron Transfer and Proton Pumping of Cytochrome c Oxidase upon the Change from the Fe^V Oxidation Level to the Fe^IV Oxidation Level Ogura, Takashi; Hirota, Shun; Proshlyakov, Denis A. Journal of the American Chemical Society, Vol. 118, Issue 23 https://doi.org/10.1021/ja951922i	journal	January 1996
A Resonance Raman Marker Band Characterizes the Slow and Fast Form of Cytochrome c Oxidase Kruse, Fabian; Nguyen, Anh Duc; Dragelj, Jovan Journal of the American Chemical Society, Vol. 143, Issue 7 https://doi.org/10.1021/jacs.0c10767	journal	February 2021
Proton translocation by cytochrome c oxidase Verkhovsky, Michael I.; Jasaitis, Audrius; Verkhovskaya, Marina L. Nature, Vol. 400, Issue 6743 https://doi.org/10.1038/22813	journal	July 1999
Ferryl and hydroxy intermediates in the reaction of oxygen with reduced cytochrome c oxidase Han, Sanghwa; Ching, Yuan-chin; Rousseau, Denis L. Nature, Vol. 348, Issue 6296 https://doi.org/10.1038/348089a0	journal	November 1990
De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure Colletier, Jacques-Philippe; Sawaya, Michael R.; Gingery, Mari Nature, Vol. 539, Issue 7627 https://doi.org/10.1038/nature19825	journal	September 2016
Determination of damage-free crystal structure of an X-ray–sensitive protein using an XFEL Hirata, Kunio; Shinzawa-Itoh, Kyoko; Yano, Naomine Nature Methods, Vol. 11, Issue 7 https://doi.org/10.1038/nmeth.2962	journal	May 2014
Concentric-flow electrokinetic injector enables serial crystallography of ribosome and photosystem II Sierra, Raymond G.; Gati, Cornelius; Laksmono, Hartawan Nature Methods, Vol. 13, Issue 1 https://doi.org/10.1038/nmeth.3667	journal	November 2015
Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade Tetreau, Guillaume; Banneville, Anne-Sophie; Andreeva, Elena A. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-14894-w	journal	March 2020
Cryo-EM structures of intermediates suggest an alternative catalytic reaction cycle for cytochrome c oxidase Kolbe, F.; Safarian, S.; Piórek, Ż. Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-27174-y	journal	November 2021
Serial femtosecond crystallography structure of cytochrome c oxidase at room temperature Andersson, Rebecka; Safari, Cecilia; Dods, Robert Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-04817-z	journal	July 2017
Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein Ciftci, Halilibrahim; Tateishi, Hiroshi; Koiwai, Kotaro Scientific Reports, Vol. 11, Issue 1 https://doi.org/10.1038/s41598-021-95236-8	journal	August 2021
Cooperative allostery and structural dynamics of streptavidin at cryogenic- and ambient-temperature Ayan, Esra; Yuksel, Busra; Destan, Ebru Communications Biology, Vol. 5, Issue 1 https://doi.org/10.1038/s42003-021-02903-7	journal	January 2022
Coupled transport of electrons and protons in a bacterial cytochromecoxidase—DFT calculated properties compared to structures and spectroscopies Noodleman, Louis; Han Du, Wen-Ge; McRee, Duncan Physical Chemistry Chemical Physics, Vol. 22, Issue 46 https://doi.org/10.1039/D0CP04848H	journal	January 2020
The catalytic cycle of cytochrome c oxidase is not the sum of its two halves Bloch, D.; Belevich, I.; Jasaitis, A. Proceedings of the National Academy of Sciences, Vol. 101, Issue 2 https://doi.org/10.1073/pnas.0306036101	journal	December 2003
Identification of conserved lipid/detergent-binding sites in a high-resolution structure of the membrane protein cytochrome c oxidase Qin, L.; Hiser, C.; Mulichak, A. Proceedings of the National Academy of Sciences, Vol. 103, Issue 44 https://doi.org/10.1073/pnas.0606149103	journal	October 2006
The proton pumping pathway of bovine heart cytochrome c oxidase Shimokata, K.; Katayama, Y.; Murayama, H. Proceedings of the National Academy of Sciences, Vol. 104, Issue 10 https://doi.org/10.1073/pnas.0611627104	journal	February 2007
Single-electron reduction of the oxidized state is coupled to proton uptake via the K pathway in Paracoccus denitrificans cytochrome c oxidase Ruitenberg, Maarten; Kannt, Aimo; Bamberg, Ernst Proceedings of the National Academy of Sciences, Vol. 97, Issue 9 https://doi.org/10.1073/pnas.080079097	journal	April 2000
The proton donor for OO bond scission by cytochrome c oxidase Gorbikova, E. A.; Belevich, I.; Wikstrom, M. Proceedings of the National Academy of Sciences, Vol. 105, Issue 31 https://doi.org/10.1073/pnas.0802512105	journal	July 2008
A peroxide bridge between Fe and Cu ions in the O2 reduction site of fully oxidized cytochrome c oxidase could suppress the proton pump Aoyama, H.; Muramoto, K.; Shinzawa-Itoh, K. Proceedings of the National Academy of Sciences, Vol. 106, Issue 7 https://doi.org/10.1073/pnas.0806391106	journal	January 2009
Crystallographic and online spectral evidence for role of conformational change and conserved water in cytochrome oxidase proton pump Liu, Jian; Qin, Ling; Ferguson-Miller, Shelagh Proceedings of the National Academy of Sciences, Vol. 108, Issue 4 https://doi.org/10.1073/pnas.1012846108	journal	January 2011
Computational study of the activated OH state in the catalytic mechanism of cytochrome c oxidase Sharma, V.; Karlin, K. D.; Wikstrom, M. Proceedings of the National Academy of Sciences, Vol. 110, Issue 42 https://doi.org/10.1073/pnas.1220379110	journal	September 2013
Characterizing the proton loading site in cytochrome c oxidase Lu, J.; Gunner, M. R. Proceedings of the National Academy of Sciences, Vol. 111, Issue 34 https://doi.org/10.1073/pnas.1407187111	journal	August 2014
Snapshot of an oxygen intermediate in the catalytic reaction of cytochrome c oxidase Ishigami, Izumi; Lewis-Ballester, Ariel; Echelmeier, Austin Proceedings of the National Academy of Sciences, Vol. 116, Issue 9 https://doi.org/10.1073/pnas.1814526116	journal	February 2019
Primary intermediate in the reaction of oxygen with fully reduced cytochrome c oxidase. Han, S. W.; Ching, Y. C.; Rousseau, D. L. Proceedings of the National Academy of Sciences, Vol. 87, Issue 7 https://doi.org/10.1073/pnas.87.7.2491	journal	April 1990
Resolution of the reaction sequence during the reduction of O2 by cytochrome oxidase. Varotsis, C.; Zhang, Y.; Appelman, E. H. Proceedings of the National Academy of Sciences, Vol. 90, Issue 1 https://doi.org/10.1073/pnas.90.1.237	journal	January 1993
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 Konstantinov, A. A.; Siletsky, S.; Mitchell, D. Proceedings of the National Academy of Sciences, Vol. 94, Issue 17 https://doi.org/10.1073/pnas.94.17.9085	journal	August 1997
Quantitative Reevaluation of the Redox Active Sites of Crystalline Bovine Heart Cytochrome c Oxidase Mochizuki, Masao; Aoyama, Hiroshi; Shinzawa-Itoh, Kyoko Journal of Biological Chemistry, Vol. 274, Issue 47 https://doi.org/10.1074/jbc.274.47.33403	journal	November 1999
A Cooperative Oxygen Binding Hemoglobin from Mycobacterium tuberculosis Yeh, Syun-Ru; Couture, Manon; Ouellet, Yannick Journal of Biological Chemistry, Vol. 275, Issue 3 https://doi.org/10.1074/jbc.275.3.1679	journal	January 2000
Time Dependence of the Catalytic Intermediates in Cytochrome c Oxidase Han, Sanghwa; Takahashi, Satoshi; Rousseau, Denis L. Journal of Biological Chemistry, Vol. 275, Issue 3 https://doi.org/10.1074/jbc.275.3.1910	journal	January 2000
The Protonation State of the Cross-linked Tyrosine during the Catalytic Cycle of Cytochrome c Oxidase Gorbikova, Elena A.; Wikström, Mårten; Verkhovsky, Michael I. Journal of Biological Chemistry, Vol. 283, Issue 50 https://doi.org/10.1074/jbc.M803511200	journal	October 2008
X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms Shimada, Atsuhiro; Etoh, Yuki; Kitoh-Fujisawa, Rika Journal of Biological Chemistry, Vol. 295, Issue 17 https://doi.org/10.1074/jbc.RA119.009596	journal	April 2020
X-ray–induced photoreduction of heme metal centers rapidly induces active-site perturbations in a protein-independent manner Pfanzagl, Vera; Beale, John H.; Michlits, Hanna Journal of Biological Chemistry, Vol. 295, Issue 39 https://doi.org/10.1074/jbc.RA120.014087	journal	September 2020
Low-barrier hydrogen bonds in proteins Hosur, M. V.; Chitra, R.; Hegde, Samarth Crystallography Reviews, Vol. 19, Issue 1 https://doi.org/10.1080/0889311X.2013.771633	journal	January 2013
Molecular Mechanism of Proton Translocation by Cytochrome c Oxidase Belevich, Ilya; Verkhovsky, Michael I. Antioxidants & Redox Signaling, Vol. 10, Issue 1 https://doi.org/10.1089/ars.2007.1705	journal	January 2008
Functions of the hydrophilic channels in protonmotive cytochrome c oxidase Rich, Peter R.; Maréchal, Amandine Journal of The Royal Society Interface, Vol. 10, Issue 86 https://doi.org/10.1098/rsif.2013.0183	journal	September 2013
CrystFEL : a software suite for snapshot serial crystallography White, Thomas A.; Kirian, Richard A.; Martin, Andrew V. Journal of Applied Crystallography, Vol. 45, Issue 2 https://doi.org/10.1107/S0021889812002312	journal	March 2012
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Nanoflow electrospinning serial femtosecond crystallography Sierra, Raymond G.; Laksmono, Hartawan; Kern, Jan Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 11, p. 1584-1587 https://doi.org/10.1107/S0907444912038152	journal	October 2012
The CCP4 suite programs for protein crystallography Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763 https://doi.org/10.1107/S0907444994003112	journal	September 1994
Cryoradiolytic reduction of crystalline heme proteins: analysis by UV-Vis spectroscopy and X-ray crystallography Beitlich, Thorsten; Kühnel, Karin; Schulze-Briese, Clemens Journal of Synchrotron Radiation, Vol. 14, Issue 1 https://doi.org/10.1107/S0909049506049806	journal	December 2006
Linac Coherent Light Source data analysis using psana Damiani, D.; Dubrovin, M.; Gaponenko, I. Journal of Applied Crystallography, Vol. 49, Issue 2 https://doi.org/10.1107/S1600576716004349	journal	March 2016
Recent developments in CrystFEL White, Thomas A.; Mariani, Valerio; Brehm, Wolfgang Journal of Applied Crystallography, Vol. 49, Issue 2 https://doi.org/10.1107/S1600576716004751	journal	March 2016
OnDA : online data analysis and feedback for serial X-ray imaging Mariani, Valerio; Morgan, Andrew; Yoon, Chun Hong Journal of Applied Crystallography, Vol. 49, Issue 3 https://doi.org/10.1107/S1600576716007469	journal	May 2016
The PDB_REDO server for macromolecular structure model optimization Joosten, Robbie P.; Long, Fei; Murshudov, Garib N. IUCrJ, Vol. 1, Issue 4 https://doi.org/10.1107/S2052252514009324	journal	May 2014
Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals Wolff, Alexander M.; Young, Iris D.; Sierra, Raymond G. IUCrJ, Vol. 7, Issue 2 https://doi.org/10.1107/S205225252000072X	journal	February 2020
High-Resolution Protein Structure Determination by Serial Femtosecond Crystallography Boutet, S.; Lomb, L.; Williams, G. J. Science, Vol. 337, Issue 6092 https://doi.org/10.1126/science.1217737	journal	May 2012
Data systems for the Linac coherent light source Thayer, J.; Damiani, D.; Ford, C. Advanced Structural and Chemical Imaging, Vol. 3, Issue 1 https://doi.org/10.1186/s40679-016-0037-7	journal	January 2017
Tyrosine Deprotonation and Associated Hydrogen Bond Rearrangements in a Photosynthetic Reaction Center Ishikita, Hiroshi PLoS ONE, Vol. 6, Issue 10 https://doi.org/10.1371/journal.pone.0026808	journal	October 2011
The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase Blomberg, Margareta R. A. Frontiers in Chemistry, Vol. 9 https://doi.org/10.3389/fchem.2021.640155	journal	April 2021

Similar Records

Snapshot of an oxygen intermediate in the catalytic reaction of cytochrome c oxidase

Journal Article · 2019 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1494322

Ishigami, Izumi; Lewis-Ballester, Ariel; Echelmeier, Austin; +17 more

Crystal structure of CO-bound cytochrome c oxidase determined by serial femtosecond X-ray crystallography at room temperature

Journal Article · 2017 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1390295

Ishigami, Izumi; Zatsepin, Nadia A.; Hikita, Masahide; +12 more

High Resolution Structure of the ba3 Cytochrome c Oxidase from Thermus thermophilus in a Lipidic Environment

Journal Article · 2012 · PLoS One · OSTI ID:1041345

Tiefenbrunn, Theresa; Liu, Wei; Chen, Ying; +4 more

Title: Structural insights into functional properties of the oxidized form of cytochrome c oxidase

Citation Formats

References (71)

Similar Records

Related Subjects