ArticleMolecular microbiology2014
The CcmFH complex is the system I holocytochrome c synthetase: engineering cytochrome c maturation independent of CcmABCDE.
Article in Molecular microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Analysis of putative heme ligands in the System I bacterial cytochromeMicrobiology spectrum · 2026Article
- From genes to function: regulation, maturation, and evolution of cytochromeApplied and environmental microbiology · 2025Review
- Article
- Recombinant Biogenesis and Analysis of Cytochrome c Species.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Architecture of the Heme-translocating CcmABCD/E complex required for Cytochrome c maturation.Nature communications · 2023Article
- AF2Complex predicts direct physical interactions in multimeric proteins with deep learning.Nature communications · 2022Article
- Maize PPR278 Functions in Mitochondrial RNA Splicing and Editing.International journal of molecular sciences · 2022Article
- Cryo-EM of CcsBA reveals the basis for cytochrome c biogenesis and heme transport.Nature chemical biology · 2022Article
- Architecture of the membrane-bound cytochrome c heme lyase CcmF.Nature chemical biology · 2021Article
- Promoting Extracellular Electron Transfer ofFrontiers in microbiology · 2021Article
- A de novo peroxidase is also a promiscuous yet stereoselective carbene transferase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Structurally Mapping Endogenous Heme in the CcmCDE Membrane Complex for Cytochrome c Biogenesis.Journal of molecular biology · 2018Article
- The thioreduction component CcmG confers efficiency and the heme ligation component CcmH ensures stereo-specificity during cytochromeThe Journal of biological chemistry · 2017Article
- Heme Trafficking and Modifications during System I Cytochrome c Biogenesis: Insights from Heme Redox Potentials of Ccm Proteins.Biochemistry · 2016Article
- Mitochondrial cytochrome c biogenesis: no longer an enigma.Trends in biochemical sciences · 2015Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome c maturation (ccm) in many bacteria, archaea and plant mitochondria requires eight membrane proteins, CcmABCDEFGH, called system I. This pathway delivers and attaches haem covalently to two cysteines (of Cys-Xxx-Xxx-Cys-His) in the cytochrome c. All models propose that CcmFH facilitates covalent attachment of haem to the apocytochrome; namely, that it is the synthetase. However, holocytochrome c synthetase activity has not been directly demonstrated for CcmFH. We report formation of holocytochromes c by CcmFH and CcmG, a periplasmic thioredoxin, independent of CcmABCDE (we term this activity CcmFGH-only). Cytochrome c produced in the absence of CcmABCDE is indistinguishable from cytochrome c produced by the full system I, with a cleaved signal sequence and two covalent bonds to haem. We engineered increased cytochrome c production by CcmFGH-only, with yields approaching those from the full system I. Three conserved histidines in CcmF (TM-His1, TM-His2 and P-His1) are required for activity, as are the conserved cysteine pairs in CcmG and CcmH. Our findings establish that CcmFH is the system I holocytochrome c synthetase. Although we discuss why this engineering would likely not replace the need for CcmABCDE in nature, these results provide unique mechanistic and evolutionary insights into cytochrome c biosynthesis.
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