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

Ishigami, Izumi; Zatsepin, Nadia A.; Hikita, Masahide; Conrad, Chelsie E.; Nelson, Garrett; Coe, Jesse D.; Basu, Shibom; Grant, Thomas D.; Seaberg, Matthew H.; Sierra, Raymond G.; Hunter, Mark S.; Fromme, Petra; Fromme, Raimund; Yeh, Syun -Ru; Rousseau, Denis L.

doi:10.1073/pnas.1705628114

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

Journal Article · Tue Jul 11 00:00:00 EDT 2017 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1705628114· OSTI ID:1390295

Ishigami, Izumi ^[1]; Zatsepin, Nadia A. ^[2]; Hikita, Masahide ^[3]; Conrad, Chelsie E. ^[4]; Nelson, Garrett ^[2]; Coe, Jesse D. ^[2]; Basu, Shibom ^[2]; Grant, Thomas D. ^[5]; Seaberg, Matthew H. ^[6]; Sierra, Raymond G. ^[6]; Hunter, Mark S. ^[6]; Fromme, Petra ^[2]; Fromme, Raimund ^[2]; Yeh, Syun -Ru ^[1]; Rousseau, Denis L. ^[1]

Albert Einstein College of Medicine, Bronx, NY (United States)
Arizona State Univ., Tempe, AZ (United States)
Albert Einstein College of Medicine, Bronx, NY (United States); Institute of Materials Structure Science, Ibaraki (Japan)
Arizona State Univ., Tempe, AZ (United States); National Cancer Institute, Frederick, MD (United States)
State Univ. of New York at Buffalo, Buffalo, NY (United States)
SLAC National Accelerator Lab., Menlo Park, CA (United States)

Here, cytochrome c oxidase (CcO), the terminal enzyme in the electron transfer chain, translocates protons across the inner mitochondrial membrane by harnessing the free energy generated by the reduction of oxygen to water. Several redox-coupled proton translocation mechanisms have been proposed, but they lack confirmation, in part from the absence of reliable structural information due to radiation damage artifacts caused by the intense synchrotron radiation. Here we report the room temperature, neutral pH (6.8), damage-free structure of bovine CcO (bCcO) in the carbon monoxide (CO)-bound state at a resolution of 2.3 Å, obtained by serial femtosecond X-ray crystallography (SFX) with an X-ray free electron laser. As a comparison, an equivalent structure was obtained at a resolution of 1.95 Å, from data collected at a synchrotron light source. In the SFX structure, the CO is coordinated to the heme a3 iron atom, with a bent Fe–C–O angle of ~142°. In contrast, in the synchrotron structure, the Fe–CO bond is cleaved; CO relocates to a new site near Cu_B, which, in turn, moves closer to the heme a₃ iron by ~0.38 Å. Structural comparison reveals that ligand binding to the heme a₃ iron in the SFX structure is associated with an allosteric structural transition, involving partial unwinding of the helix-X between heme a and a₃, thereby establishing a communication linkage between the two heme groups, setting the stage for proton translocation during the ensuing redox chemistry.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-76SF00515; GM098799; GM115773; GM095583; CHE-1404929; ABI-1565180; STC-1231306

OSTI ID:: 1390295

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, Issue 30; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 36 works

Citation information provided by
Web of Science

References (53)

Redox-Controlled Proton Gating in Bovine Cytochrome c Oxidase Egawa, Tsuyoshi; Yeh, Syun-Ru; Rousseau, Denis L. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1817 https://doi.org/10.1016/j.bbabio.2012.06.384	journal	October 2012
Cheetah : software for high-throughput reduction and analysis of serial femtosecond X-ray diffraction data Barty, Anton; Kirian, Richard A.; Maia, Filipe R. N. C. Journal of Applied Crystallography, Vol. 47, Issue 3 https://doi.org/10.1107/S1600576714007626	journal	May 2014
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
Proton pathways, ligand binding and dynamics of the catalytic site in haem-copper oxygen reductases: a comparison between the three families Pereira, Manuela M.; Teixeira, Miguel Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1655 https://doi.org/10.1016/j.bbabio.2003.06.003	journal	April 2004
The Whole Structure of the 13-Subunit Oxidized Cytochrome c Oxidase at 2.8 A Tsukihara, T.; Aoyama, H.; Yamashita, E. Science, Vol. 272, Issue 5265 https://doi.org/10.1126/science.272.5265.1136	journal	May 1996
Reaction Mechanism of Cytochrome c Oxidase Yoshikawa, Shinya; Shimada, Atsuhiro Chemical Reviews, Vol. 115, Issue 4 https://doi.org/10.1021/cr500266a	journal	January 2015
Structural Changes and Proton Transfer in Cytochrome c Oxidase Vilhjálmsdóttir, Jóhanna; Johansson, Ann-Louise; Brzezinski, Peter Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep12047	journal	August 2015
Crystallographic and Spectroscopic Studies of Peroxide-derived Myoglobin Compound II and Occurrence of Protonated Fe ^IV –O Hersleth, Hans-Petter; Uchida, Takeshi; Røhr, Åsmund K. Journal of Biological Chemistry, Vol. 282, Issue 32 https://doi.org/10.1074/jbc.M701948200	journal	June 2007
Looking for the minimum common denominator in haem–copper oxygen reductases: Towards a unified catalytic mechanism Pereira, Manuela M.; Sousa, Filipa L.; Veríssimo, Andreia F. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1777, Issue 7-8 https://doi.org/10.1016/j.bbabio.2008.05.441	journal	July 2008
Effective Pumping Proton Collection Facilitated by a Copper Site (Cu _B ) of Bovine Heart Cytochrome c Oxidase, Revealed by a Newly Developed Time-resolved Infrared System Kubo, Minoru; Nakashima, Satoru; Yamaguchi, Satoru Journal of Biological Chemistry, Vol. 288, Issue 42 https://doi.org/10.1074/jbc.M113.473983	journal	August 2013
Structural Characterization of Synthetic and Protein-Bound Porphyrins in Terms of the Lowest-Frequency Normal Coordinates of the Macrocycle Jentzen, Walter; Song, Xing-Zhi; Shelnutt, John A. The Journal of Physical Chemistry B, Vol. 101, Issue 9 https://doi.org/10.1021/jp963142h	journal	February 1997
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
Interactions of Cu _B with Carbon Monoxide in Cytochrome c Oxidase: Origin of the Anomalous Correlation between the Fe–CO and C–O Stretching Frequencies Egawa, Tsuyoshi; Haber, Jonah; Fee, James A. The Journal of Physical Chemistry B, Vol. 119, Issue 27 https://doi.org/10.1021/acs.jpcb.5b04444	journal	June 2015
Structure at 2.8 Å resolution of cytochrome c oxidase from Paracoccus denitrificans Iwata, So; Ostermeier, Christian; Ludwig, Bernd Nature, Vol. 376, Issue 6542 https://doi.org/10.1038/376660a0	journal	August 1995
Femtosecond X-ray protein nanocrystallography Chapman, Henry N.; Fromme, Petra; Barty, Anton Nature, Vol. 470, Issue 7332, p. 73-77 https://doi.org/10.1038/nature09750	journal	February 2011
New Perspectives on Proton Pumping in Cellular Respiration Wikström, Mårten; Sharma, Vivek; Kaila, Ville R. I. Chemical Reviews, Vol. 115, Issue 5 https://doi.org/10.1021/cr500448t	journal	February 2015
Radiation damage in protein crystals is reduced with a micron-sized X-ray beam Sanishvili, R.; Yoder, D. W.; Pothineni, S. B. Proceedings of the National Academy of Sciences, Vol. 108, Issue 15 https://doi.org/10.1073/pnas.1017701108	journal	March 2011
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
Proton-Coupled Electron Transfer in Cytochrome Oxidase Kaila, Ville R. I.; Verkhovsky, Michael I.; Wikström, Mårten Chemical Reviews, Vol. 110, Issue 12 https://doi.org/10.1021/cr1002003	journal	December 2010
When X-rays modify the protein structure: radiation damage at work Carugo, Oliviero; Carugo, Kristina Djinović Trends in Biochemical Sciences, Vol. 30, Issue 4 https://doi.org/10.1016/j.tibs.2005.02.009	journal	April 2005
Computer simulation of water in cytochrome c oxidase Zheng, Xuehe; Medvedev, Dmitry M.; Swanson, Jessica Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1557 https://doi.org/10.1016/S0005-2728(03)00002-1	journal	March 2003
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
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
Mechanisms of Ligand Recognition in Myoglobin Springer, Barry A.; Sligar, Stephen G.; Olson, John S. Chemical Reviews, Vol. 94, Issue 3 https://doi.org/10.1021/cr00027a007	journal	May 1994
On the role of the K-proton transfer pathway in cytochrome c oxidase Branden, M.; Sigurdson, H.; Namslauer, A. Proceedings of the National Academy of Sciences, Vol. 98, Issue 9 https://doi.org/10.1073/pnas.081088398	journal	April 2001
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
Photodissociation and recombination of carbonmonoxy cytochrome oxidase: Dynamics from picoseconds to kiloseconds Einarsdottir, Olof; Dyer, R. Brian; Lemon, Douglas D. Biochemistry, Vol. 32, Issue 45 https://doi.org/10.1021/bi00096a011	journal	November 1993
Redox-Controlled Proton Gating in Bovine Cytochrome c Oxidase Egawa, Tsuyoshi; Yeh, Syun-Ru; Rousseau, Denis L. PLoS ONE, Vol. 8, Issue 5 https://doi.org/10.1371/journal.pone.0063669	journal	May 2013
Combined Microspectrophotometric and Crystallographic Examination of Chemically Reduced and X-ray Radiation-Reduced Forms of Cytochrome ba ₃ Oxidase from Thermus thermophilus : Structure of the Reduced Form of the Enzyme ^† Liu, Bin; Chen, Ying; Doukov, Tzanko Biochemistry, Vol. 48, Issue 5 https://doi.org/10.1021/bi801759a	journal	February 2009
Coupled proton and electron transfer reactions in cytochrome oxidase Gennis, Robert, B. Frontiers in Bioscience, Vol. 9, Issue 1-3 https://doi.org/10.2741/1237	journal	January 2004
Radiation damage in macromolecular crystallography: what is it and why should we care? Garman, Elspeth F. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910008656	journal	March 2010
Diversity and Conservation of Interactions for Binding Heme in b-Type Heme Proteins Schneider, Sabine; Marles-Wright, Jon; Sharp, Katherine H. ChemInform, Vol. 38, Issue 36 https://doi.org/10.1002/chin.200736275	journal	September 2007
Redox-Dependent Conformational Changes in Cytochrome c Oxidase Suggest a Gating Mechanism for Proton Uptake Qin, Ling; Liu, Jian; Mills, Denise A. Biochemistry, Vol. 48, Issue 23 https://doi.org/10.1021/bi9001387	journal	June 2009
Kinetic Pathways and Barriers for Ligand Binding to Myoglobin Olson, John S.; Phillips, George N. Journal of Biological Chemistry, Vol. 271, Issue 30 https://doi.org/10.1074/jbc.271.30.17593	journal	July 1996
Structural Changes and Proton Transfer in Cytochrome c Oxidase Vilhjálmsdóttir, Jóhanna; Johansson, Ann-Louise; Brzezinski, Peter Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1857 https://doi.org/10.1016/j.bbabio.2016.04.320	journal	August 2016
Reactions of cytochrome oxidase with oxygen and carbon monoxide Gibson, Qh; Greenwood, C. Biochemical Journal, Vol. 86, Issue 3 https://doi.org/10.1042/bj0860541	journal	March 1963
How does Radiation Damage in Protein Crystals Depend on X-Ray Dose? Sliz, Piotr; Harrison, Stephen C.; Rosenbaum, Gerd Structure, Vol. 11, Issue 1 https://doi.org/10.1016/S0969-2126(02)00910-3	journal	January 2003
Rate theories and puzzles of hemeprotein kinetics Frauenfelder, H.; Wolynes, P. Science, Vol. 229, Issue 4711 https://doi.org/10.1126/science.4012322	journal	July 1985
The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process Tsukihara, T.; Shimokata, K.; Katayama, Y. Proceedings of the National Academy of Sciences, Vol. 100, Issue 26 https://doi.org/10.1073/pnas.2635097100	journal	December 2003
Proton translocation in cytochrome c oxidase: Insights from proton exchange kinetics and vibrational spectroscopy Ishigami, Izumi; Hikita, Masahide; Egawa, Tsuyoshi Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1847, Issue 1 https://doi.org/10.1016/j.bbabio.2014.09.008	journal	January 2015
Overview of the CCP4 suite and current developments. Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.52322	text	January 2011
The Mg ²⁺ -containing Water Cluster of Mammalian Cytochrome c Oxidase Collects Four Pumping Proton Equivalents in Each Catalytic Cycle Yano, Naomine; Muramoto, Kazumasa; Shimada, Atsuhiro Journal of Biological Chemistry, Vol. 291, Issue 46 https://doi.org/10.1074/jbc.M115.711770	journal	September 2016
Redox-Coupled Crystal Structural Changes in Bovine Heart Cytochrome c Oxidase Yoshikawa, S. Science, Vol. 280, Issue 5370 https://doi.org/10.1126/science.280.5370.1723	journal	June 1998
Cytochrome c oxidase: 25 years of the elusive proton pump Wikström, Mårten Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1655 https://doi.org/10.1016/j.bbabio.2003.07.013	journal	April 2004
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
Bovine cytochrome c oxidase structures enable O ₂ reduction with minimization of reactive oxygens and provide a proton-pumping gate Muramoto, Kazumasa; Ohta, Kazuhiro; Shinzawa-Itoh, Kyoko Proceedings of the National Academy of Sciences, Vol. 107, Issue 17 https://doi.org/10.1073/pnas.0910410107	journal	April 2010
Diffraction before destruction Chapman, Henry N.; Caleman, Carl; Timneanu, Nicusor Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 369, Issue 1647 https://doi.org/10.1098/rstb.2013.0313	journal	July 2014
Proton-Pumping Mechanism of Cytochrome c Oxidase Yoshikawa, Shinya; Muramoto, Kazumasa; Shinzawa-Itoh, Kyoko Annual Review of Biophysics, Vol. 40, Issue 1 https://doi.org/10.1146/annurev-biophys-042910-155341	journal	June 2011
Diversity and conservation of interactions for binding heme in b-type heme proteins Schneider, Sabine; Marles-Wright, Jon; Sharp, Katherine H. Natural Product Reports, Vol. 24, Issue 3 https://doi.org/10.1039/b604186h	journal	January 2007
Resonance Raman detection of iron-carbonmonoxy stretching and iron-carbon-oxygen bending vibrations in sterically hindered carbonmonoxy "strapped hemes". A structural probe of iron-carbon-oxygen distortion Yu, Nai Teng; Kerr, Ellen A.; Ward, Brian Biochemistry, Vol. 22, Issue 19 https://doi.org/10.1021/bi00288a028	journal	September 1983
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
Analysis of the kinetic barriers for ligand binding to sperm whale myoglobin using site-directed mutagenesis and laser photolysis techniques. Carver, T. E.; Rohlfs, R. J.; Olson, J. S. Journal of Biological Chemistry, Vol. 265, Issue 32 https://doi.org/10.1016/S0021-9258(17)45475-5	journal	November 1990
Studies of the primary oxygen intermediate in the reaction of fully reduced cytochrome oxidase. Blackmore, R. S.; Greenwood, C.; Gibson, Q. H. Journal of Biological Chemistry, Vol. 266, Issue 29 https://doi.org/10.1016/S0021-9258(18)54989-9	journal	October 1991

Cited By (9)

Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets Kaczara, Patrycja; Przyborowski, Kamil; Mohaissen, Tasnim International Journal of Molecular Sciences, Vol. 22, Issue 7 https://doi.org/10.3390/ijms22073584	journal	March 2021
Radiation chemists look at damage in redox proteins induced by X-rays Wherland, Scot; Pecht, Israel Proteins: Structure, Function, and Bioinformatics, Vol. 86, Issue 8 https://doi.org/10.1002/prot.25521	journal	May 2018
Macromolecular Nanocrystal Structural Analysis with Electron and X-Rays: A Comparative Review Khakurel, Krishna P.; Angelov, Borislav; Andreasson, Jakob Molecules, Vol. 24, Issue 19 https://doi.org/10.3390/molecules24193490	journal	September 2019
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
X-ray free-electron laser: opportunities for drug discovery Cheng, Robert; Abela, Rafael; Hennig, Michael Acta Crystallographica Section A Foundations and Advances, Vol. 74, Issue a1 https://doi.org/10.1107/s0108767318095570	journal	July 2018
Recent Advances in Ultrafast Structural Techniques Sciaini, Germán Applied Sciences, Vol. 9, Issue 7 https://doi.org/10.3390/app9071427	journal	April 2019
X-ray free electron laser: opportunities for drug discovery Cheng, Robert K. Y.; Abela, Rafael; Hennig, Michael Essays in Biochemistry, Vol. 61, Issue 5 https://doi.org/10.1042/ebc20170031	journal	November 2017
Cytochrome c oxidase structures suggest a four-state stochastic pump mechanism Palese, Luigi Leonardo Physical Chemistry Chemical Physics, Vol. 21, Issue 9 https://doi.org/10.1039/c8cp07365a	journal	January 2019
Insights into functions of the H channel of cytochrome c oxidase from atomistic molecular dynamics simulations Sharma, Vivek; Jambrina, Pablo G.; Kaukonen, Markus Proceedings of the National Academy of Sciences, Vol. 114, Issue 48 https://doi.org/10.1073/pnas.1708628114	journal	November 2017

Similar Records

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

Journal Article · Mon Feb 11 00:00:00 EST 2019 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1390295

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

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

Journal Article · Sat Sep 16 00:00:00 EDT 2023 · Nature Communications · OSTI ID:1390295

Ishigami, Izumi; Sierra, Raymond G.; Su, Zhen; +11 more

Structure-Function of the Cytochrome b₆f Complex of Oxygenic Photosynthesis

Book · Thu Mar 20 00:00:00 EDT 2014 · OSTI ID:1390295

Cramer, W. A.; Yamashita, E.; Baniulis, D.; +2 more

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
bioenergetics
X-ray free electron laser
crystallography
cytochrome c oxidase
serial femtosecond crystallography

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

Citation Formats

References (53)

Cited By (9)

Similar Records

Related Subjects