Cytochrome c maturation: a complex pathway for a simple task?
Post-translational maturation of c-type cytochromes involves covalent attachment of haem to the apocytochrome polypeptide by two thioether bonds. In bacteria, haem attachment occurs in the periplasm, after the separate translocation of haem and the polypeptide across the cytoplasmic membrane. In Escherichia coli, delivery and attachment of the cofactor requires eight or nine specific proteins, which are believed to be organized in a membrane protein complex. After transport across the membrane, haem is attached covalently to the haem chaperone CcmE in an unusual way at a single histidine residue. However, haem binding to CcmE is transient and is succeeded by a further transfer to apocytochrome c. Both haem binding to and release from CcmE involve integral membrane proteins, CcmC and CcmF respectively, which carry a conserved tryptophan-rich motif in a periplasmic domain. Apocytochrome c polypeptides are synthesized as precursors and reach the periplasm by sec-dependent translocation. There they are prepared for haem binding by reduction of the cysteine residues in the motif Cys-Xaa-Xaa-Cys-His, which is characteristic of such proteins. This reduction is achieved in a thio-reduction pathway, whereby electrons are passed from cytoplasmic thioredoxin to the transmembrane protein DsbD, across the membrane, and on to the specific reductases CcmG/CcmH. The merging of the haem delivery and the thio-reduction pathways leads to the stereospecific insertion of haem into various type c cytochromes.
Institut für Mikrobiologie, Departement Biologie, ETH Zentrum, CH-8092 Zürich, Switzerland. lthoeny@micro.biol.ethz.ch
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Thöny-Meyer
D000595:Amino Acid Sequence; D001059:Apoproteins / Q000378:metabolism; D001665:Binding Sites; D003574:Cytochrome c Group / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045304:Cytochromes c; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006418:Heme / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D001059:Apoproteins; D003574:Cytochrome c Group; D006418:Heme; D045304:Cytochromes c