Analysis of putative heme ligands in the System I bacterial cytochrome c biogenesis heme transporter, CcmCD

Heme is a critical co-factor for proteins with essential biological functions including gas sensing and electron transport. However, free or unbound heme is highly toxic to cells. To mitigate toxicity, there must be specific pathways to move heme in cells. While heme transport proteins have been identified genetically, their mechanism of transport remains elusive. The bacterial cytochrome c biogenesis pathways, Systems I and II, are excellent model systems to investigate heme transport. We compare the System I heme transporter, CcmCD, with the System II heme transporter, CcsBA. Analysis of putative transmembrane localized heme axial ligands in CcmCD determined that heme liganding is not required for heme transport. In contrast, CcsBA requires transmembrane heme axial liganding for function. Thus, the bacterial cytochrome c biogenesis heme transporters have different mechanisms, suggesting that additional mechanisms of transmembrane transport may be uncovered via experimental analysis of other heme transporters in prokaryotes and eukaryotes.