The thioreduction component CcmG confers efficiency and the heme ligation component CcmH ensures stereo-specificity during cytochrome c maturation

Verissimo, Andreia F.; Khalfaoui-Hassani, Bahia; Hwang, Josephine; Steimle, Stefan; Selamoglu, Nur; Sanders, Carsten; Khatchikian, Camilo E.; Daldal, Fevzi

doi:10.1074/jbc.m117.794586

Title: The thioreduction component CcmG confers efficiency and the heme ligation component CcmH ensures stereo-specificity during cytochrome c maturation

Journal Article · Tue Jun 20 00:00:00 EDT 2017 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.m117.794586· OSTI ID:1535361

Verissimo, Andreia F. ^[1]; Khalfaoui-Hassani, Bahia ^[1]; Hwang, Josephine ^[1]; Steimle, Stefan ^[1]; Selamoglu, Nur ^[1]; Sanders, Carsten ^[2]; Khatchikian, Camilo E. ^[3]; Daldal, Fevzi ^[1]

Pennsylvania State Univ., University Park, PA (United States). Dept. of Biology
Univ. of Kutztown, Kutztown, PA (United States). Dept. of Physical Sciences
Univ. of Texas at El Paso, TX (United States). Dept of Biological Sciences

In many Gram-negative bacteria, including Rhodobacter capsulatus, cytochrome c maturation (Ccm) is carried out by a membrane-integral machinery composed of nine proteins (CcmA to I). During this process, the periplasmic thiol-disulfide oxidoreductase DsbA is thought to catalyze the formation of a disulfide bond between the Cys residues at the apocytochrome c heme binding site (CXXCH). Subsequently, a Ccm-specific thioreductive pathway involving CcmG and CcmH reduces this disulfide bond to allow covalent heme ligation. Currently, the sequence of thioredox reactions occurring between these components and apocytochrome c, and the identity of their active Cys residues are unknown. In this work, we first investigated protein-protein interactions among the apocytochrome c, CcmG, and the heme ligation components CcmF, CcmH, and CcmI. We found that they all interact with each other, forming a CcmFGHI-apocytochrome c complex. Using purified wild-type CcmG, CcmH, and apocytochrome c, as well as their respective Cys mutant variants we determined the rates of thiol-disulfide exchange reactions between selected pairs of Cys residues from these proteins. We established that CcmG can efficiently reduce the disulfide bond of apocytochrome c and also resolve a mixed disulfide bond formed between apocytochrome c and CcmH. We further show that C45 of CcmH and C34 of apocytochrome c are most likely to form this mixed disulfide bond, which is consistent with the stereo-specificity of the heme-apocytochrome c ligation reaction. We conclude that CcmG confers efficiency, and CcmH ensures stereo-specificity during Ccm, and present a comprehensive model for thioreduction reactions that lead to heme-apocytochrome c ligation.

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Research Organization:: Univ. of Pennsylvania, Philadelphia, PA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: FG02-91ER20052

OSTI ID:: 1535361

Journal Information:: Journal of Biological Chemistry, Vol. 292, Issue 32; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 13 works

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References (50)

Cytochrome c biogenesis: the Ccm system Sanders, Carsten; Turkarslan, Serdar; Lee, Dong-Woo Trends in Microbiology, Vol. 18, Issue 6 https://doi.org/10.1016/j.tim.2010.03.006	journal	June 2010
Structure and mechanisms of the DsbB–DsbA disulfide bond generation machine Inaba, Kenji; Ito, Koreaki Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1783, Issue 4 https://doi.org/10.1016/j.bbamcr.2007.11.006	journal	April 2008
Structure and multistate function of the transmembrane electron transporter CcdA Williamson, Jessica A.; Cho, Seung-Hyun; Ye, Jiqing Nature Structural & Molecular Biology, Vol. 22, Issue 10 https://doi.org/10.1038/nsmb.3099	journal	September 2015
Control of DegP-Dependent Degradation of c-Type Cytochromes by Heme and the Cytochrome c Maturation System in Escherichia coli Gao, T.; O'Brian, M. R. Journal of Bacteriology, Vol. 189, Issue 17 https://doi.org/10.1128/JB.00656-07	journal	July 2007
A Strategic Protein in Cytochrome c Maturation : THREE-DIMENSIONAL STRUCTURE OF CcmH AND BINDING TO APOCYTOCHROME c Di Matteo, Adele; Gianni, Stefano; Schininà, M. Eugenia Journal of Biological Chemistry, Vol. 282, Issue 37 https://doi.org/10.1074/jbc.M702702200	journal	July 2007
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 Laemmli, U. K. Nature, Vol. 227, Issue 5259, p. 680-685 https://doi.org/10.1038/227680a0	journal	August 1970
AtCCMH, an essential component of the c-type cytochrome maturation pathway in Arabidopsis mitochondria, interacts with apocytochrome c Meyer, E. H.; Giege, P.; Gelhaye, E. Proceedings of the National Academy of Sciences, Vol. 102, Issue 44 https://doi.org/10.1073/pnas.0503473102	journal	October 2005
Biochemical properties and catalytic domain structure of the CcmH protein from Escherichia coli Zheng, Xue-Ming; Hong, Jing; Li, Hai-Yin Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1824, Issue 12 https://doi.org/10.1016/j.bbapap.2012.06.017	journal	December 2012
Helix swapping leads to dimerization of the N-terminal domain of the c -type cytochrome maturation protein CcmH from Escherichia coli Ahuja, Umesh; Rozhkova, Anna; Glockshuber, Rudolf FEBS Letters, Vol. 582, Issue 18 https://doi.org/10.1016/j.febslet.2008.07.007	journal	July 2008
Cytochrome c biogenesis System I: An intricate process catalyzed by a maturase supercomplex? Verissimo, Andreia F.; Daldal, Fevzi Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1837, Issue 7 https://doi.org/10.1016/j.bbabio.2014.03.003	journal	July 2014
Cytochrome c Biogenesis: Mechanisms for Covalent Modifications and Trafficking of Heme and for Heme-Iron Redox Control Kranz, R. G.; Richard-Fogal, C.; Taylor, J. -S. Microbiology and Molecular Biology Reviews, Vol. 73, Issue 3 https://doi.org/10.1128/MMBR.00001-09	journal	August 2009
The Heme Chaperone ApoCcmE Forms a Ternary Complex with CcmI and Apocytochrome c Verissimo, Andreia F.; Mohtar, Mohamad A.; Daldal, Fevzi Journal of Biological Chemistry, Vol. 288, Issue 9 https://doi.org/10.1074/jbc.M112.440024	journal	January 2013
Evolutionary domain fusion expanded the substrate specificity of the transmembrane electron transporter DsbD Katzen, F. The EMBO Journal, Vol. 21, Issue 15 https://doi.org/10.1093/emboj/cdf405	journal	August 2002
The Cytochrome c Maturation Components CcmF, CcmH, and CcmI Form a Membrane-integral Multisubunit Heme Ligation Complex Sanders, Carsten; Turkarslan, Serdar; Lee, Dong-Woo Journal of Biological Chemistry, Vol. 283, Issue 44 https://doi.org/10.1074/jbc.M805413200	journal	August 2008
The Escherichia coli CcmG protein fulfils a specific role in cytochrome c assembly Reid, Eleanor; Cole, Jeff; Eaves, Deborah J. Biochemical Journal, Vol. 355, Issue 1 https://doi.org/10.1042/bj3550051	journal	February 2001
Recognition and binding of apocytochrome c to P. aeruginosa CcmI, a component of cytochrome c maturation machinery Di Silvio, Eva; Di Matteo, Adele; Malatesta, Francesco Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1834, Issue 8 https://doi.org/10.1016/j.bbapap.2013.04.027	journal	August 2013
Structural Basis and Kinetics of DsbD-Dependent Cytochrome c Maturation Stirnimann, Christian U.; Rozhkova, Anna; Grauschopf, Ulla Structure, Vol. 13, Issue 7 https://doi.org/10.1016/j.str.2005.04.014	journal	July 2005
Overexpression of ccl1−2 can bypass the need for the putative apocytochrome chaperone CycH during the biogenesis of c-type cytochromes: Suppressors of CycH-null mutants overexpress the ccl1-2 operon Deshmukh, Meenal; May, Matthew; Zhang, Yan Molecular Microbiology, Vol. 46, Issue 4 https://doi.org/10.1046/j.1365-2958.2002.03212.x	journal	November 2002
Overproduction of CcmG and CcmFHRc Fully Suppresses the c-Type Cytochrome Biogenesis Defect of Rhodobacter capsulatus CcmI-Null Mutants Sanders, C.; Deshmukh, M.; Astor, D. Journal of Bacteriology, Vol. 187, Issue 12 https://doi.org/10.1128/JB.187.12.4245-4256.2005	journal	June 2005
Formation and properties of mixed disulfides between thioredoxin reductase from Escherichia coli and thioredoxin: Evidence that cysteine-138 functions to initiate dithiol-disulfide interchange and to accept the reducing equivalent from reduced flavin Veine, Donna M.; Mulrooney, Scott B.; Wang, Pan-Fen Protein Science, Vol. 7, Issue 6 https://doi.org/10.1002/pro.5560070621	journal	June 1998
Cytochrome c assembly Mavridou, Despoina A. I.; Ferguson, Stuart J.; Stevens, Julie M. IUBMB Life, Vol. 65, Issue 3 https://doi.org/10.1002/iub.1123	journal	January 2013
A Cytochrome b ₅₆₂ Variant with a c -Type Cytochrome C XX CH Heme-binding Motif as a Probe of the Escherichia coli Cytochrome c Maturation System Allen, James W. A.; Barker, Paul D.; Ferguson, Stuart J. Journal of Biological Chemistry, Vol. 278, Issue 52 https://doi.org/10.1074/jbc.M307196200	journal	October 2003
A thioreduction pathway tethered to the membrane for periplasmic cytochromes c biogenesis; in vitro and in vivo studies Monika, Elizabeth M.; Goldman, Barry S.; Beckman, Diana L. Journal of Molecular Biology, Vol. 271, Issue 5 https://doi.org/10.1006/jmbi.1997.1227	journal	September 1997
Expression of prokaryotic and eukaryotic cytochromes c in Escherichia coli Sanders, Carsten; Lill, Holger Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1459, Issue 1 https://doi.org/10.1016/S0005-2728(00)00122-5	journal	July 2000
Characterization of the Escherichia coli CcmH protein reveals new insights into the redox pathway required for cytochrome c maturation Fabianek, Renata Annette; Hofer, Thomas; Thöny-Meyer, L. Archives of Microbiology, Vol. 171, Issue 2 https://doi.org/10.1007/s002030050683	journal	January 1999
Prediction of pKa and redox properties in the thioredoxin superfamily Moutevelis, Efrosini; Warwicker, Jim Protein Science, Vol. 13, Issue 10 https://doi.org/10.1110/ps.04804504	journal	October 2004
Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei Schlecker, Tanja; Comini, Marcelo A.; Melchers, Johannes Biochemical Journal, Vol. 405, Issue 3 https://doi.org/10.1042/BJ20070259	journal	July 2007
Novel Rhodobacter capsulatus genes required for the biogenesis of various c-type cytochromes Deshmukh, Meenal; Brasseur, Gael; Daldal, Fevzi Molecular Microbiology, Vol. 35, Issue 1 https://doi.org/10.1046/j.1365-2958.2000.01683.x	journal	January 2000
During Cytochrome c Maturation CcmI Chaperones the Class I Apocytochromes until the Formation of Their b -Type Cytochrome Intermediates Verissimo, Andreia F.; Shroff, Namita P.; Daldal, Fevzi Journal of Biological Chemistry, Vol. 290, Issue 27 https://doi.org/10.1074/jbc.M115.652818	journal	May 2015
Oxidation−Reduction Properties of Disulfide-Containing Proteins of the Rhodobacter capsulatus Cytochrome c Biogenesis System ^† Setterdahl, Aaron T.; Goldman, Barry S.; Hirasawa, Masakazu Biochemistry, Vol. 39, Issue 33 https://doi.org/10.1021/bi000663t	journal	August 2000
Kinetics of the Intramolecular Disulfide Exchange Between the Periplasmic Domains of DsbD Rozhkova, Anna; Glockshuber, Rudi Journal of Molecular Biology, Vol. 367, Issue 4 https://doi.org/10.1016/j.jmb.2006.12.033	journal	April 2007
Kinetic and thermodynamic studies on the disulfide-bond reducing potential of hydrogen sulfide Vasas, Anita; Dóka, Éva; Fábián, István Nitric Oxide, Vol. 46 https://doi.org/10.1016/j.niox.2014.12.003	journal	April 2015
Cytochrome c : Occurrence and Functions Bertini, Ivano; Cavallaro, Gabriele; Rosato, Antonio Chemical Reviews, Vol. 106, Issue 1 https://doi.org/10.1021/cr050241v	journal	January 2006
Catalytic Mechanism of DsbA and Its Comparison with That of Protein Disulfide Isomerase Darby, Nigel J.; Creighton, Thomas E. Biochemistry, Vol. 34, Issue 11 https://doi.org/10.1021/bi00011a012	journal	March 1995
Two Snapshots of Electron Transport across the Membrane: INSIGHTS INTO THE STRUCTURE AND FUNCTION OF DsbD Cho, Seung-Hyun; Beckwith, Jon Journal of Biological Chemistry, Vol. 284, Issue 17 https://doi.org/10.1074/jbc.M900651200	journal	March 2009
The CcmFH complex is the system I holocytochrome c synthetase: engineering cytochrome c maturation independent of CcmABCDE : CcmFH is the system I holocytochrome San Francisco, Brian; Sutherland, Molly C.; Kranz, Robert G. Molecular Microbiology, Vol. 91, Issue 5 https://doi.org/10.1111/mmi.12510	journal	January 2014
Structural and functional characterization of CcmG from Pseudomonas aeruginosa, a key component of the bacterial cytochrome c maturation apparatus Matteo, Adele Di; Calosci, Nicoletta; Gianni, Stefano Proteins: Structure, Function, and Bioinformatics, Vol. 78, Issue 10 https://doi.org/10.1002/prot.22733	journal	May 2010
A Pivotal Heme-transfer Reaction Intermediate in Cytochrome c Biogenesis Mavridou, Despoina A. I.; Stevens, Julie M.; Mönkemeyer, Leonie Journal of Biological Chemistry, Vol. 287, Issue 4 https://doi.org/10.1074/jbc.M111.313692	journal	November 2011
The Sec translocon mediated protein transport in prokaryotes and eukaryotes Denks, Kärt; Vogt, Andreas; Sachelaru, Ilie Molecular Membrane Biology, Vol. 31, Issue 2-3 https://doi.org/10.3109/09687688.2014.907455	journal	March 2014
Structure and Function of DsbA, a Key Bacterial Oxidative Folding Catalyst Shouldice, Stephen R.; Heras, Begoña; Walden, Patricia M. Antioxidants & Redox Signaling, Vol. 14, Issue 9 https://doi.org/10.1089/ars.2010.3344	journal	May 2011
A Stable Mixed Disulfide between Thioredoxin Reductase and Its Substrate, Thioredoxin: Preparation and Characterization ^† Wang, Pan-Fen; Veine, Donna M.; Ahn, Sung Ho Biochemistry, Vol. 35, Issue 15 https://doi.org/10.1021/bi9526793	journal	January 1996
Reactivity of Thioredoxin as a Protein Thiol-Disulfide Oxidoreductase Cheng, Zhiyong; Zhang, Jinfeng; Ballou, David P. Chemical Reviews, Vol. 111, Issue 9 https://doi.org/10.1021/cr100006x	journal	September 2011
Crystal structures of E. coli CcmG and its mutants reveal key roles of the N-terminal β-sheet and the fingerprint region Ouyang, Nan; Gao, Yong-Guang; Hu, Hong-Yu Proteins: Structure, Function, and Bioinformatics, Vol. 65, Issue 4 https://doi.org/10.1002/prot.21184	journal	October 2006
Compensatory thio-redox interactions between DsbA, CcdA and CcmG unveil the apocytochrome c holdase role of CcmG during cytochrome c maturation Turkarslan, Serdar; Sanders, Carsten; Ekici, Seda Molecular Microbiology, Vol. 70, Issue 3 https://doi.org/10.1111/j.1365-2958.2008.06441.x	journal	November 2008
The Dithiol:Disulfide Oxidoreductases DsbA and DsbB of Rhodobacter capsulatus Are Not Directly Involved in Cytochrome c Biogenesis, but Their Inactivation Restores the Cytochrome c Biogenesis Defect of CcdA-Null Mutants Deshmukh, M.; Turkarslan, S.; Astor, D. Journal of Bacteriology, Vol. 185, Issue 11 https://doi.org/10.1128/JB.185.11.3361-3372.2003	journal	June 2003
Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions Netto, Luis Eduardo S.; de Oliveira, Marcos Antonio; Tairum, Carlos A. Free Radical Research, Vol. 50, Issue 2 https://doi.org/10.3109/10715762.2015.1120864	journal	January 2016
Protein Disulfide Bond Formation in the Periplasm: Determination of the In Vivo Redox State of Cysteine Residues Denoncin, Katleen; Nicolaes, Valérie; Cho, Seung-Hyun Methods in Molecular Biology https://doi.org/10.1007/978-1-62703-245-2_20	book	November 2012
Structure of CcmG/DsbE at 1.14 Å Resolution Edeling, Melissa A.; Guddat, Luke W.; Fabianek, Renata A. Structure, Vol. 10, Issue 7 https://doi.org/10.1016/s0969-2126(02)00794-3	journal	July 2002
Mitochondrial thiol oxidase Erv1: both shuttle cysteine residues are required for its function with distinct roles Ang, Swee Kim; Zhang, Mengqi; Lodi, Tiziana Biochemical Journal, Vol. 460, Issue 2 https://doi.org/10.1042/bj20131540	journal	May 2014
Membrane-Spanning and Periplasmic Segments of CcmI Have Distinct Functions during Cytochrome c Biogenesis in Rhodobacter capsulatus Sanders, C.; Boulay, C.; Daldal, F. Journal of Bacteriology, Vol. 189, Issue 3 https://doi.org/10.1128/jb.01441-06	journal	November 2006

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