TRANSMEMBRANE HEME DELIVERY SYSTEMS

Heme proteins play pivotal roles in a wealth of biological processes. Despite this, the molecular mechanisms by which heme traverses bilayer membranes for use in biosynthetic reactions are unknown. The biosynth esis of c-type cytochromes requires that heme is transported to the ba cterial periplasm or mitochondrial intermembrane space where it is cov alently ligated to two reduced cysteinyl residues of the apocytochrome , Results herein suggest that a family of integral membrane proteins i n prokaryotes, protozoans, and plants act as transmembrane heme delive ry systems for the biogenesis of c-type cytochromes. The complete topo logy of a representative from each of the three subfamilies was experi mentally determined. Key histidinyl residues and a conserved tryptopha n-rich region (designated the WWD domain) are positioned at the site o f cytochrome c assembly for all three subfamilies. These histidinyl re sidues were shown to be essential for function in one of the subfamili es, an ABC transporter encoded by helABCD. We believe that a directed heme delivery pathway is vital for the synthesis of cytochromes c, whe reby heme iron is protected from oxidation via ligation to histidinyl residues within the delivery proteins.