title: Transmembrane heme delivery systems.
abstract: 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 biosynthesis of c-type cytochromes requires that heme is transported to the bacterial periplasm or mitochondrial intermembrane space where it is covalently ligated to two reduced cysteinyl residues of the apocytochrome. Results herein suggest that a family of integral membrane proteins in prokaryotes, protozoans, and plants act as transmembrane heme delivery systems for the biogenesis of c-type cytochromes. The complete topology of a representative from each of the three subfamilies was experimentally determined. Key histidinyl residues and a conserved tryptophan-rich region (designated the WWD domain) are positioned at the site of cytochrome c assembly for all three subfamilies. These histidinyl residues were shown to be essential for function in one of the subfamilies, an ABC transporter encoded by helABCD. We believe that a directed heme delivery pathway is vital for the synthesis of cytochromes c, whereby heme iron is protected from oxidation via ligation to histidinyl residues within the delivery proteins.
authors.affiliation: Department of Biology, Washington University, One Brookings Drive, St. Louis, MO 63130, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Goldman
authors.forename: D L
authors.initials: DL
authors.lastname: Beck
authors.forename: E M
authors.initials: EM
authors.lastname: Monika
authors.forename: R G
authors.initials: RG
authors.lastname: Kranz
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002736:Chloroplasts / Q000737:chemistry; D006418:Heme / Q000378:metabolism*; D006420:Hemeproteins / Q000737:chemistry*; D006639:Histidine; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D010940:Plant Proteins; D011506:Proteins / Q000737:chemistry*; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014364:Tryptophan
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; C109582:HelA protein, bacteria; C112241:HelB protein, Rhodobacter capsulatus; C112242:HelC protein, bacteria; C112243:HelD protein, Rhodobacter capsulatus; D006420:Hemeproteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010940:Plant Proteins; D011506:Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C075103:ccsA protein, protozoan; D006418:Heme; D006639:Histidine; D014364:Tryptophan