Prototype of a Heme Chaperone Essential for Cytochrome c Maturation

Schulz, Henk; Hennecke, Hauke; Thöny‐Meyer, Linda

doi:10.1126/science.281.5380.1197

Cited by 177 publications

(257 citation statements)

References 19 publications

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“…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). It has been established that CcmC further delivers haem to another membrane protein, CcmE, considered to be a haem chaperone that passes haem to a haem lyase complex (comprising the CcmF protein) before covalent binding of the haem prosthetic group to apocytochromes c (Schulz et al, 1998(Schulz et al, , 1999(Schulz et al, , 2000. CcmC has been postulated to be a cytoplasmto-periplasm haem exporter Goldman et al, 1998) and has been demonstrated to interact with the CcmAB ABC transporter (Goldman et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2003

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The cytoplasmic membrane protein CcmC is, together with other Ccm proteins, a component for the maturation of c-type cytochromes in Gram-negative bacteria. A Pseudomonas fluorescens ATCC 17400 ccmC mutant is cytochrome c-deficient and shows considerably reduced production of the two siderophores pyoverdine and quinolobactin, paralleled by a general inability to utilize various iron sources, with the exception of haem. The ccmC mutant accumulates in a 5-aminolevulinic acid-dependent synthesis a reddish, fluorescent pigment identified as protoporphyrin IX. As a consequence a visA phenotype similar to that of a ferrochelatase-deficient hemH mutant characterized by drastically reduced growth upon light exposure was observed for the ccmC mutant. The defect of iron–protoporphyrin formation was further demonstrated by the failure of ccmC cell-free proteinase K-treated extracts to stimulate the growth of a haem auxotrophic hemH indicator strain, compared to similarly prepared wild-type extracts. In addition, the ccmC mutant did not sustain hemH growth in cross-feeding experiments while the wild-type did. Significantly reduced resistance to oxidative stress mediated by haem-containing catalases was observed for the ccmC mutant. A double hemH ccmC mutant could not be obtained in the presence of external haem without the hemH gene in trans, indicating that the combination of the two mutations is lethal. It was concluded that CcmC, apart from its known function in cytochrome c biogenesis, plays a role in haem biosynthesis. A function in the regulatory co-ordination of iron acquisition via siderophores, iron insertion into porphyrin via ferrochelatase and iron–protoporphyrin export for cytochrome c formation is predicted.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2003

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“…CcmCDE are involved in heme delivery. CcmC is required for the covalent attachment of heme to the heme chaperone CcmE (10)(11)(12). CcmF has been proposed to form a bacterial cytochrome c heme lyase complex together with CcmH (13).…”

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confidence: 99%

AtCCMH, an essential component of thec-type cytochrome maturation pathway inArabidopsismitochondria, interacts with apocytochromec

Meyer

Giegé

Gelhaye

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The maturation of c-type cytochromes requires the covalent ligation of the heme cofactor to reduced cysteines of the CXXCH motif of apocytochromes. In contrast to mitochondria of other eukaryotes, plant mitochondria follow a pathway close to that found in ␣-and ␥-proteobacteria. We identified a nuclear-encoded protein, AtCCMH, the Arabidopsis thaliana ortholog of bacterial CcmH͞CycL proteins. In bacteria, CcmH and the thioredoxin CcmG are components of a periplasmic thio-reduction pathway proposed to maintain the apocytochrome c cysteines in a reduced state. AtCCMH is located exclusively in mitochondria. AtCCMH is an integral protein of the inner membrane with the conserved RCXXC motif facing the intermembrane space. Reduction assays show that the cysteine thiols in the RCXXC motif of AtCCMH can form a disulfide bond that can be reduced by enzymatic thiol reductants.

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“…1A) comprises the membrane-bound proteins CcmABCDEFGH. CcmA, CcmB, and CcmC form an ABC-type transporter, the function of which is unknown (20,21), although it is known that CcmC, together with CcmE, is involved in heme delivery to the cytochrome c heme lyase complex consisting of CcmFH (22)(23)(24)(25)(26). Reduction of the cysteinyls of the Cys-Xxx-Xxx-Cys-His motif prior to heme insertion is accomplished by CcmG and CcmH, but it is not clear whether the electrons flow from CcmG by means of CcmH, or from CcmH via CcmG, to the apo-cytochrome (27,28).…”

mentioning

confidence: 99%

Structural Basis of Redox-coupled Protein Substrate Selection by the Cytochrome c Biosynthesis Protein ResA

Crow

Acheson

Brun

et al. 2004

Journal of Biological Chemistry

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Post-translational maturation of cytochromes c involves the covalent attachment of heme to the Cys-XxxXxx-Cys-His motif of the apo-cytochrome. For this process, the two cysteines of the motif must be in the reduced state. In bacteria, this is achieved by dedicated, membrane-bound thiol-disulfide oxidoreductases with a high reducing power, which are essential components of cytochrome c maturation systems and are also linked to cellular disulfide-bond formation machineries. Here we report high-resolution structures of oxidized and reduced states of a soluble, functional domain of one such oxidoreductase, ResA, from Bacillus subtilis. The structures elucidate the structural basis of the protein's high reducing power and reveal the largest redox-coupled conformational changes observed to date in any thioredoxin-like protein. These redox-coupled changes alter the protein surface and illustrate how the redox state of ResA predetermines to which substrate it binds. Furthermore, a polar cavity, present only in the reduced state, may confer specificity to recognize apo-cytochrome c. The described features of ResA are likely to be general for bacterial cytochrome c maturation systems.

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Prototype of a Heme Chaperone Essential for Cytochrome c Maturation

Cited by 177 publications

References 19 publications

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

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

AtCCMH, an essential component of thec-type cytochrome maturation pathway inArabidopsismitochondria, interacts with apocytochromec

Structural Basis of Redox-coupled Protein Substrate Selection by the Cytochrome c Biosynthesis Protein ResA

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