Abstract
Cytochrome c maturation (CCM), a posttranslational modification involving covalent attachment of heme to polypeptides (apocyt c), is essential for the activity and cellular function of cytochromes c. Here, we identify and substantiate CcmB as heme translocase in bacteria. When in excess, CcmB expels intracellular heme into the periplasm and thus is detrimental to the cell. We then show that complexation with CcmACD ensures heme translocated by CcmB to be used for CCM only. Moreover, structural analysis and atomistic molecular dynamics simulations reveal that CcmB absorbs heme from the membrane to a heme pocket formed in the dimer interface of the transmembrane helix-bundles. These data, collectively by providing detailed insights into the conformational landscape of CcmB during heme entry, fill in the missing link in our understanding of the heme translocation for CCM.