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Review
. 2011 Nov;278(22):4170-8.
doi: 10.1111/j.1742-4658.2011.08376.x. Epub 2011 Oct 20.

Cytochrome C Biogenesis System I

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Free PMC article
Review

Cytochrome C Biogenesis System I

Julie M Stevens et al. FEBS J. .
Free PMC article

Abstract

Cytochromes c are widespread respiratory proteins characterized by the covalent attachment of heme. The formation of c-type cytochromes requires, in all but a few exceptional cases, the formation of two thioether bonds between the two cysteine sulfurs in a -CXXCH- motif in the protein and the vinyl groups of heme. The vinyl groups of the heme are not particularly activated and therefore the addition reaction does not physiologically occur spontaneously in cells. There are several diverse post-translational modification systems for forming these bonds. Here, we describe the complex multiprotein cytochrome c maturation (Ccm) system (in Escherichia coli comprising the proteins CcmABCDEFGH), also called System I, that performs the heme attachment. System I is found in plant mitochondria, archaea and many Gram-negative bacteria; the systems found in other organisms and organelles are described elsewhere in this minireview series.

Figures

Fig. 1
Fig. 1
The cytochrome c maturation System I. The Ccm proteins (in blue) are all integral membrane proteins or are membrane-anchored with soluble domains in the periplasm (with the exception of CcmA, which hydrolyses ATP in the cytoplasm). The structures of the soluble domains of CcmE, CcmG and the N-terminal domain of CcmH have been solved and are shown on the periplasmic side (the Protein Data Bank accession numbers are 1LIZ [53], 2B1K [54] and 2HL7 [21], respectively). The structure of a paralog of the C-terminal domain of CcmH, NrfG, is also shown (Protein Data Bank accession number: 2E2E [23]). The holocytochrome c shown is from Paracoccus denitrificans (Protein Data Bank accession number: 155C). CcmH in Escherichia coli is a fusion of two proteins that occur separately in other organisms (CcmH and CcmI, labeled N-CcmH and C-CcmH). The apocytochrome c protein is shown in red, as is the holocytochrome c produced when heme (shown in black) becomes covalently attached. The cysteine residues, assumed to be involved in reducing the –CXXCH– motif in the apocytochrome, are shown in yellow.
Fig. 2
Fig. 2
(A) Heme attachment to cytochrome c indicating the thioether bonds formed at the 2-vinyl and 4-vinyl heme positions to the two cysteine residues on the protein. The N′ and C′ orientations of the two cysteines are shown. (B) Heme attachment to the histidine side chain of CcmE [36].
Fig. 3
Fig. 3
Possible interaction networks for CcmG, CcmH and apocytochrome c showing either direct (A) or indirect (B) provision of reductant from CcmG to apocytochrome c. The arrows indicate the possible pathways of reductant transfer and the dotted lines represent protein–protein interactions. (A) In the case of direct provision of reductant, CcmG would reduce the –CXXCH– motif in apocytochrome c. N-CcmH and C-CcmH would be involved in interactions with each other and with the apocytochrome c to facilitate heme attachment. (B) In the case of indirect provision of reductant, CcmG would reduce N-CcmH which, in turn, would reduce apocytochrome c.

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References

    1. Barker PD, Ferguson SJ. Still a puzzle: why is haem covalently attached in c-type cytochromes? Structure. 1999;7:R281–R290. - PubMed
    1. Stevens JM, Daltrop O, Allen JW, Ferguson SJ. C-type cytochrome formation: chemical and biological enigmas. Acc Chem Res. 2004;37:999–1007. - PubMed
    1. Allen JW, Jackson AP, Rigden DJ, Willis AC, Ferguson SJ, Ginger ML. Order within a mosaic distribution of mitochondrial c-type cytochrome biogenesis systems? FEBS J. 2008;275:2385–2402. - PubMed
    1. Bertini I, Cavallaro G, Rosato A. Evolution of mitochondrial-type cytochrome c domains and of the protein machinery for their assembly. J Inorg Biochem. 2007;101:1798–1811. - PubMed
    1. Simon J, Hederstedt L. Composition and function of cytochrome c biogenesis System II. FEBS J. 2011;278:4179–4188. - PubMed

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