9.B.14.3.1
Cytochrome c biogenesis protein, CcsBA (936 aas; 10 TMSs; 14 TMSs predicted by the WHAT program (Frawley and Kranz, 2009).  May be a bifunctional protein with heme transport (export from the cytoplasm to the periplasm) and attachment to apocytochrome c (cytochrome c synthetase) activities.  Two heme binding sites have been identified in a homologue, one in the membrane and one on the external surface (on the periplasmic side of the membrane) (Sutherland et al. 2018). Mendez et al. 2022 described cryo-EM structures of CcsBA, which, as noted above, is a bifunctional heme transporter and cytochrome c (cyt c) synthase. Models built from the cryo-EM densities show that CcsBA is trapped with heme in two conformations, closed and open states. The closed state has heme located solely at a transmembrane (TM) site, with a large periplasmic domain oriented such that access of heme to the cytochrome acceptor is prevented. The open conformation contains two heme moieties, one in the TM-heme site and another in an external site (P-heme site). The presence of heme in the periplasmic site at the base of a chamber induces a large conformational shift that exposes the heme for reaction with apocytochrome c (apocyt c). Consistent with these structures, in vivo and in vitro cyt c synthase studies suggest a mechanism for transfer of the periplasmic heme to cytochrome (Mendez et al. 2022).