Mmicular mechanisms of cytochrome c biogenesis: three distinct systems

Abstract

SummaryThe past 10 years have heralded remarkable progress in the understanding of the biogenesis of c-type cytochromes. The hallmark of c-type cytochrome synthesis is the covalent ligation of haem vinyl groups to two cysteinyl residues of the apocytochrome (at a CysXxx-Yyy-Cys-His signature motif). From genetic, genomic and biochemical studies, it is clear that three distinct systems have evolved in nature to assemble this ancient protein. In this review, common principles of assembly for all systems and the molecular mechanisms predicted for each system are summarized. Prokaryotes, plant mitochondria and chloroplasts use either system I or II, which are each predicted to use dedicated mechanisms for haem delivery, apocytochrome ushering and thioreduction. Accessory proteins of systems I and II co-ordinate the positioning of these two substrates at the membrane surface for covalent ligation. The third system has evolved specifically in mitochondria of fungi, invertebrates and vertebrates. For system III, a pivotal role is played by an enzyme called cytochrome c haem lyase (CCHL) in the mitochondrial intermembrane space.

Co-ordination of iron acquisition, iron porphyrin chelation and iron–protoporphyrin export via the cytochrome c biogenesis protein CcmC in Pseudomonas fluorescens

“…The importance of the cytoplasmic membrane protein CcmC in the biogenesis of c-type cytochromes in Gramnegative bacteria has been clearly established, but its role is still controversial (Thöny-Meyer, 1997; Kranz et al, 1998;Page & Ferguson, 1999;Cook & Poole, 2000;Schulz et al, 2000). Obviously, absence of CcmC causes a range of defects which are not all due to the absence of c-type cytochromes (Gaballa et al, 1998).…”

“…We isolated one mutant of P. fluorescens ATCC 17400 with a transposon insertion in the ccmC gene that showed greatly reduced production of PVD, an impaired maturation of the PVD chromophore, together with a decreased capacity to utilize this particular siderophore (Gaballa et al, 1996(Gaballa et al, , 1998Baysse et al, 2002). The product of this gene, the cytoplasmic membrane protein CcmC, is primarily involved in the biogenesis of c-type cytochromes (Thöny-Meyer, 1997; Kranz et al, 1998). CcmC binds haem in the periplasm, probably via two conserved histidines in the first and the third periplasmic loops, the interaction being stabilized by hydrophobic amino acids in the second periplasmic loop, mostly composed of tryptophan residues Schulz et al, 2000).…”

The Acidic Nature of the CcmG Redox-Active Center Is Important for CytochromecMaturation inEscherichia coli

“…This binding requires the formation of two thioether bonds between the vinyl groups of heme and two cysteines in the conserved Cys-X-X-Cys-His motif of the apocytochrome. Three different posttranslational systems have evolved to facilitate cytochrome c formation in vivo (15). The most complicated of these systems, system I, is found in many gram-negative bacteria.…”

Extracytoplasmic prosthetic group ligation to apoproteins: maturation of c‐type cytochromes

“…How, and when, the haem-Fe (depicted in black with a red dot) is reduced before its ligation to the c apocytochromes is unknown, except that Cyc2p in yeast might be involved in this step (Bernard et al ., 2005). mitochondria of fungi, invertebrates and vertebrates (Kranz et al ., 1998). First, as the compartment where c apocytochromes are synthesized is not identical to where c holocytochromes function, translocation across the membrane is required, and is mediated by the Sec complex in SI and SII prokaryotes, and the TOM complex in SIII organelles (Fig.…”

“…1D). Surprisingly, the CcsAB-dependent E. coli system does not require a CcmG-like component thought to be involved in apocytochrome c thio-reduction (Kranz et al ., 1998;Thony-Meyer, 2002). This finding is very intriguing, because a CcmG homologue, CcsX, is also required for c -type cytochromes maturation in SII organisms, including H. pylori and B. pertussis (Beckett et al ., 2000;Le Brun et al, 2000).…”