FIG. 1.
Current model of Cyt c biogenesis in R. capsulatus. Pre-apo-Cyt c produced in the cytoplasm are translocated across the membrane via the Sec-dependent secretory pathway. Their signal peptides (SP) are either processed or used as N-terminal membrane anchors. Disulfide bonds are assumed to be formed within the cysteines of the conserved apo-Cyt c heme binding motif CxxCH and then possibly chaperoned via CcmI to the Cyt c maturation site. CcdA shuttles electrons across the membrane to the thioreduction component CcmHRc via CcmG. CcmHRc is thought to reduce the heme binding site disulfides prior to heme attachment. The heme cofactor (H) is synthesized in the cytoplasm from δ-amino levulinic acid (δ-ALA), putatively transported to the periplasm via the ATP-binding cassette (ABC) transporter CcmAB, and covalently ligated to CcmE via CcmCD, with WWD referring to the putative heme binding motif. CcmE is postulated to provide the heme to the putative heme lyase component CcmF, which is believed to attach it covalently and stereospecifically to the reduced apo-Cyt c. According to this model, CcmI-null mutants are not able to produce any holo-Cyt c, because apo-Cyt c is not delivered efficiently to the maturation site, as they probably are degraded rapidly. Hence, overproduction of CcmF and CcmHRc can alleviate the need for apo-Cyt c chaperoning and protection function of CcmI. Arrows refer to electron (e-) transfer steps, and ? indicates hypothetical steps. The bottom portion depicts the proposed interactions between CcmI, CcmG, CcmF, CcmHRc and CcmE, forming a hypothetical Cyt c biogenesis “core complex” in Rhodobacter capsulatus. This model proposes that apo-Cyt c interacts with CcmI as part of a multisubunit protein complex including CcmF and CcmHRc.