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• W1966587300 abstract "Proper functioning of the mitochondrion requires the orchestrated assembly of respiratory complexes with their cofactors. Cytochrome c, an essential electron carrier in mitochondria and a critical component of the apoptotic pathway, contains a heme cofactor covalently attached to the protein at a conserved CXXCH motif. Although it has been known for more than two decades that heme attachment requires the mitochondrial protein holocytochrome c synthase (HCCS), the mechanism remained unknown. We purified membrane-bound human HCCS with endogenous heme and in complex with its cognate human apocytochrome c. Spectroscopic analyses of HCCS alone and complexes of HCCS with site-directed variants of cytochrome c revealed the fundamental steps of heme attachment and maturation. A conserved histidine in HCCS (His154) provided the key ligand to the heme iron. Formation of the HCCS:heme complex served as the platform for interaction with apocytochrome c. Heme was the central molecule mediating contact between HCCS and apocytochrome c. A conserved histidine in apocytochrome c (His19 of CXXCH) supplied the second axial ligand to heme in the trapped HCCS:heme:cytochrome c complex. We also examined the substrate specificity of human HCCS and converted a bacterial cytochrome c into a robust substrate for the HCCS. The results allow us to describe the molecular mechanisms underlying the HCCS reaction." @default.
• W1966587300 created "2016-06-24" @default.
• W1966587300 creator A5052123021 @default.
• W1966587300 creator A5057882145 @default.
• W1966587300 creator A5065401548 @default.
• W1966587300 date "2012-11-12" @default.
• W1966587300 modified "2023-10-06" @default.
• W1966587300 title "Human mitochondrial holocytochrome <i>c</i> synthase’s heme binding, maturation determinants, and complex formation with cytochrome <i>c</i>" @default.
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• W1966587300 doi "https://doi.org/10.1073/pnas.1213897109" @default.
• W1966587300 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3587199" @default.
• W1966587300 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23150584" @default.
• W1966587300 hasPublicationYear "2012" @default.
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