The mitochondrial cytochrome c N-terminal region is critical for maturation by holocytochrome c synthase
Stevens JM., Zhang Y., Muthuvel G., Sam KA., Allen JWA., Ferguson SJ.
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. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.