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Molecular Basis Behind Inability of Mitochondrial Holocytochrome c Synthase to Mature Bacterial Cytochromes.
- Source :
-
Journal of Biological Chemistry . 8/19/2016, Vol. 291 Issue 34, p17523-17534. 12p. - Publication Year :
- 2016
-
Abstract
- Mitochondrial holocytochrome c synthase (HCCS) is required for cytochrome c (cyt c) maturation and therefore respiration. HCCS efficiently attaches heme via two thioethers to CXXCH of mitochondrial but not bacterial cyt c even though they are functionally conserved. This inability is due to residues in the bacterial cyt c N terminus, but the molecular basis is unknown. Human cyts c with deletions of single residues in α helix-1, which mimic bacterial cyt c, are poorly matured by human HCCS. Focusing on ΔM13 cyt c, we co-purified this variant with HCCS, demonstrating that HCCS recognizes the bacterial- like cytochrome. Although an HCCS-WT cyt c complex contains two covalent links, HCCS-ΔM13 cyt c contains only one thioether attachment. Using multiple approaches, we show that the single attachment is to the second thiol of C15SQC18H, indicating thatα helix-1 is required for positioning the first cysteine for covalent attachment, whereas the histidine of CXXCH positions the second cysteine. Modeling of the N-terminal structure suggested that the serine residue (of CSQCH) would be anchored where the first cysteine should be inΔM13cyt c. An engineered cyt c with a CQCH motif in the ΔM13 background is matured at higher levels (2-3-fold), providing further evidence for α helix-1 positioning the first cysteine. Bacterial cyt c biogenesis pathways (Systems I and II) appear to recognize simply the CXXCH motif, not requiring α helix-1. Results here explain mechanistically how HCCS (System III) requires an extended region adjacent to CXXCH for maturation. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CYTOCHROME c
*CYTOCHROMES
*MITOCHONDRIA
*HEME
*SYNTHASES
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 291
- Issue :
- 34
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 117622761
- Full Text :
- https://doi.org/10.1074/jbc.M116.741231