Cytochrome c biogenesis: mechanisms for covalent modifications and trafficking of heme and for heme-iron redox control
- PMID: 19721088
- PMCID: PMC2738134
- DOI: 10.1128/MMBR.00001-09
Cytochrome c biogenesis: mechanisms for covalent modifications and trafficking of heme and for heme-iron redox control
Abstract
Heme is the prosthetic group for cytochromes, which are directly involved in oxidation/reduction reactions inside and outside the cell. Many cytochromes contain heme with covalent additions at one or both vinyl groups. These include farnesylation at one vinyl in hemes o and a and thioether linkages to each vinyl in cytochrome c (at CXXCH of the protein). Here we review the mechanisms for these covalent attachments, with emphasis on the three unique cytochrome c assembly pathways called systems I, II, and III. All proteins in system I (called Ccm proteins) and system II (Ccs proteins) are integral membrane proteins. Recent biochemical analyses suggest mechanisms for heme channeling to the outside, heme-iron redox control, and attachment to the CXXCH. For system II, the CcsB and CcsA proteins form a cytochrome c synthetase complex which specifically channels heme to an external heme binding domain; in this conserved tryptophan-rich "WWD domain" (in CcsA), the heme is maintained in the reduced state by two external histidines and then ligated to the CXXCH motif. In system I, a two-step process is described. Step 1 is the CcmABCD-mediated synthesis and release of oxidized holoCcmE (heme in the Fe(+3) state). We describe how external histidines in CcmC are involved in heme attachment to CcmE, and the chemical mechanism to form oxidized holoCcmE is discussed. Step 2 includes the CcmFH-mediated reduction (to Fe(+2)) of holoCcmE and ligation of the heme to CXXCH. The evolutionary and ecological advantages for each system are discussed with respect to iron limitation and oxidizing environments.
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References
-
- Ahuja, U., A. Rozhkova, R. Glockshuber, L. Thony-Meyer, and O. Einsle. 2008. Helix swapping leads to dimerization of the N-terminal domain of the c-type cytochrome maturation protein CcmH from Escherichia coli. FEBS Lett. 5822779-2786. - PubMed
-
- Ahuja, U., and L. Thony-Meyer. 2003. Dynamic features of a heme delivery system for cytochrome C maturation. J. Biol. Chem. 27852061-52070. - PubMed
-
- Allen, J. W., P. D. Barker, O. Daltrop, J. M. Stevens, E. J. Tomlinson, N. Sinha, Y. Sambongi, and S. J. Ferguson. 2005. Why isn't ‘standard’ heme good enough for c-type and d1-type cytochromes? Dalton Trans. 20053410-3418. - PubMed
-
- Allen, J. W., P. D. Barker, and S. J. Ferguson. 2003. A cytochrome b562 variant with a c-type cytochrome CXXCH heme-binding motif as a probe of the Escherichia coli cytochrome c maturation system. J. Biol. Chem. 27852075-52083. - PubMed
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