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Probing why trypanosomes assemble atypical cytochromecwith an AxxCH haem-binding motif instead of CxxCH

Ginger, Michael L., Sam, Katharine A. and Allen, James W. A. (2012) Probing why trypanosomes assemble atypical cytochromecwith an AxxCH haem-binding motif instead of CxxCH. Biochemical Journal, 448 (2). pp. 253-260. ISSN 0264-6021

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Mitochondrial cytochromes c and c1 are core components of the respiratory chain of all oxygen-respiring eukaryotes. These proteins contain haem, covalently bound to the polypeptide in a catalysed post-translational modification. In all eukaryotes, except members of the protist phylum Euglenozoa, haem attachment is to the cysteine residues of a CxxCH haem-binding motif. In the Euglenozoa, which include medically relevant trypanosomatid parasites, haem attachment is to a single cysteine residue in an AxxCH haem-binding motif. Moreover, genes encoding known c-type cytochrome biogenesis machineries are all absent from trypanosomatid genomes, indicating the presence of a novel biosynthetic apparatus. In the present study, we investigate expression and maturation of cytochrome c with a typical CxxCH haem-binding motif in the trypanosomatids Crithidia fasciculata and Trypanosoma brucei. Haem became attached to both cysteine residues of the haem-binding motif, indicating that, in contrast with previous hypotheses, nothing prevents formation of a CxxCH cytochrome c in euglenozoan mitochondria. The cytochrome variant was also able to replace the function of wild-type cytochrome c in T. brucei. However, the haem attachment to protein was not via the stereospecifically conserved linkage universally observed in natural c-type cytochromes, suggesting that the trypanosome cytochrome c biogenesis machinery recognized and processed only the wild-type single-cysteine haem-binding motif. Moreover, the presence of the CxxCH cytochrome c resulted in a fitness cost in respiration. The level of cytochrome c biogenesis in trypanosomatids was also found to be limited, with the cells operating at close to maximum capacity.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Schools: School of Applied Sciences
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Depositing User: Michael Ginger
Date Deposited: 10 May 2016 07:14
Last Modified: 28 Aug 2021 12:03


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