ArticleThe Journal of biological chemistry2014
Mechanisms of mitochondrial holocytochrome c synthase and the key roles played by cysteines and histidine of the heme attachment site, Cys-XX-Cys-His.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Multi-omics landscape and functional validation of HCCS in breast cancer: from pan-cancer immunometabolic characterization to regulating tumor proliferation.Frontiers in genetics · 2026Article
- Mechanisms of heme transport in the mitochondria.Biochemical Society transactions · 2025Review
- FAM136A depletion induces mitochondrial stress and reduces mitochondrial membrane potential and ATP production.FEBS open bio · 2025Article
- Biogenesis of CytochromesACS infectious diseases · 2025Article
- HCCS Serves as Potential Prognostic Biomarker and Therapeutic Target in Human Breast Cancer.International journal of breast cancer · 2025Article
- Structural Insights into Mechanisms Underlying Mitochondrial and Bacterial Cytochrome c Synthases.Biomolecules · 2024Article
- Biogenesis of cytochromesbioRxiv : the preprint server for biology · 2024Article
- Recurrent evolutionary switches of mitochondrial cytochrome c maturation systems in Archaeplastida.Nature communications · 2024Article
- Structural basis of membrane machines that traffick and attach heme to cytochromes.The Journal of biological chemistry · 2023Article
- Genetically Encoded Fluorescent Probe for Detection of Heme-Induced Conformational Changes in Cytochrome c.Biosensors · 2023Article
- Investigation of the Molecular Mechanisms of the Eukaryotic Cytochrome-Biomolecules · 2022Article
- Calpain-mediated protein targets in cardiac mitochondria following ischemia-reperfusion.Scientific reports · 2022Article
- Review
- Architecture of the membrane-bound cytochrome c heme lyase CcmF.Nature chemical biology · 2021Article
- In vitro reconstitution reveals major differences between human and bacterial cytochrome c synthases.eLife · 2021Article
- Review
- Article
- Biosynthesis of Single Thioether c-Type Cytochromes Provides Insight into Mechanisms Intrinsic to Holocytochrome c Synthase (HCCS).Biochemistry · 2017Article
- Engineered holocytochromeProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Molecular Basis Behind Inability of Mitochondrial Holocytochrome c Synthase to Mature Bacterial Cytochromes: DEFINING A CRITICAL ROLE FOR CYTOCHROME c α HELIX-1.The Journal of biological chemistry · 2016Article
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7 authors.
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Abstract
Mitochondrial cytochrome c assembly requires the covalent attachment of heme by thioether bonds between heme vinyl groups and a conserved CXXCH motif of cytochrome c/c1. The enzyme holocytochrome c synthase (HCCS) binds heme and apocytochrome c substrate to catalyze this attachment, subsequently releasing holocytochrome c for proper folding to its native structure. We address mechanisms of assembly using a functional Escherichia coli recombinant system expressing human HCCS. Human cytochrome c variants with individual cysteine, histidine, double cysteine, and triple cysteine/histidine substitutions (of CXXCH) were co-purified with HCCS. Single and double mutants form a complex with HCCS but not the triple mutant. Resonance Raman and UV-visible spectroscopy support the proposal that heme puckering induced by both thioether bonds facilitate release of holocytochrome c from the complex. His-19 (of CXXCH) supplies the second axial ligand to heme in the complex, the first axial ligand was previously shown to be from HCCS residue His-154. Substitutions of His-19 in cytochrome c to seven other residues (Gly, Ala, Met, Arg, Lys, Cys, and Tyr) were used with various approaches to establish other roles played by His-19. Three roles for His-19 in HCCS-mediated assembly are suggested: (i) to provide the second axial ligand to the heme iron in preparation for covalent attachment; (ii) to spatially position the two cysteinyl sulfurs adjacent to the two heme vinyl groups for thioether formation; and (iii) to aid in release of the holocytochrome c from the HCCS active site. Only H19M is able to carry out these three roles, albeit at lower efficiencies than the natural His-19.
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