The mitochondrial cytochromecN-terminal region is critical for maturation by holocytochromecsynthase

Authors:
  • YZYulin Zhang
    Yulin Zhang
  • GMGajanthan Muthuvel
    Gajanthan Muthuvel
  • KSKatharine A. Sam
    Katharine A. Sam
  • JAJames W.A. Allen
    James W.A. Allen
  • SFStuart J. Ferguson
    Stuart J. Ferguson
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Abstract
The covalent attachment of heme to mitochondrial cytochrome c is catalysed by holocytochrome c synthase (HCCS, also called heme lyase). How HCCS functions and recognises the substrate apocytochrome is unknown. Here we have examined HCCS recognition of a chimeric substrate comprising a short mitochondrial cytochrome c N-terminal region with the C-terminal sequence, including the CXXCH heme-binding motif, of a bacterial cytochrome c that is not otherwise processed by HCCS. Heme attachment to the chimera demonstrates the importance of the N-terminal region of the cytochrome. A series of variants of a mitochondrial cytochrome c with amino acid replacements in the N-terminal region have narrowed down the specificity determinants, providing insight into HCCS substrate recognition.
Funding Information
  • Biotechnology and Biological Sciences Research Council (BB/H017887/1, BB/D019753/1)

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