Advertisement

Tetrapyrroles pp 149-159 | Cite as

Heme Transport and Incorporation into Proteins

  • Linda Thöny-Meyer
Part of the Molecular Biology Intelligence Unit book series (MBIU)

Abstract

Heme proteins are located in different compartments and organelles of pro- and eukaryotic cells. For their biosynthesis and assembly heme needs to be delivered to the polypeptides at the correct location. As heme is a hydrophobic molecule, it readily partitions into membranes and is bound to proteins, and the concentration of the free molecule in cells is extremely low. Heme is synthesized from the precursor 5-aminolevulinic acid, with the last step taking place in mitochondria in animals and fungi, and the plastid in plants. Some cells have the capability of taking heme up from the environment. The question therefore arises, how is heme transported across membranes and cellular compartments to its target proteins? The assembly of heme with these proteins is rather specific, and in many cases even stereospecific. For type c-type cytochromes, which bind heme covalendy, specialized maturation systems have evolved that catalyze heme incorporation. It is likely that other heme proteins also need appropriate assembly factors for heme insertion. The current knowledge of intracellular heme transport and the biogenesis of heme-containing proteins is limited, and has only recently been recognized as an attractive field of research.

Keywords

Heme Protein Heme Binding Free Heme Shewanella Putrefaciens Heme Uptake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Vincent SH, Gradi RW, Shaklai N et al. The influence of heme-binding proteins in heme-catalyzed oxidations. Arch Biochem Biophys 1988; 265:539–550.CrossRefPubMedGoogle Scholar
  2. 2.
    Thöny-Meyer L. Biogenesis of respiratory cytochromes in bacteria. Microbiol Mol Biol Rev 1997; 61:337–376.PubMedGoogle Scholar
  3. 3.
    Thöny-Meyer L. Haem-polypeptide interactions during cytochrome c maturation. Biochim Biophys Acta 2000; 1459:316–324.CrossRefPubMedGoogle Scholar
  4. 4.
    Xie Z, Merchant S. A novel pathway for cytochromes c biogenesis in chloroplasts. Biochim Biophys Acta 1998; 1365:309–318.CrossRefPubMedGoogle Scholar
  5. 5.
    Page MD, Sambongi Y, Ferguson SJ. Contrasting routes of c-type cytochrome assembly in mitochondria, chloroplasts and bacteria. Trends Biochem Sci 1998; 23:103–108.CrossRefPubMedGoogle Scholar
  6. 6.
    Kranz RG, Beckett CS, Goldman BS. Genomic analyses of bacterial respiratory and cytochrome c assembly systems: Bordetella as a model for the system II cytochrome c biogenesis pathway. Res Microbiol 2002; 153:1–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Kranz R, Lill R, Goldman B et al. Molecular mechanisms of cytochrome c biogenesis: Three distinct systems. Mol Microbiol 1998; 29:383–396.CrossRefPubMedGoogle Scholar
  8. 8.
    Allen JW, Daltrop O, Stevens JM et al. C-type cytochromes: Diverse structures and biogenesis systems pose evolutionary problems. Philos Trans R Soc Lond B Biol Sci 2003; 358(1429):255–266.CrossRefPubMedGoogle Scholar
  9. 9.
    Hansson M, Hederstedt L. Purification and characterisation of a water-soluble ferrochelatase from Bacillus subtilis. Eur J Biochem 1994; 220:201–208.CrossRefPubMedGoogle Scholar
  10. 10.
    O’Brian MR, Thöny-Meyer L. Biochemistry, regulation and genomics of heme biosynthesis in prokaryotes. Advances Microbial Physiol 2002; 46:257–318.CrossRefGoogle Scholar
  11. 11.
    Sassa S, Kappas A. Disorders of heme production and catabolism. In: Handin RI, Lux SE, Stossel TP, eds. Blood: Principles and Practice of Hematology. Philadelphia: J.B. Lippincott Company, 1995:1473–1523.Google Scholar
  12. 12.
    Pettigrew GW, Moore GR. Cytochromes c. Biological Aspects. New York: Springer-Verlag, 1987.Google Scholar
  13. 13.
    Schulz H, Hennecke H, Thöny-Meyer L. Prototype of a heme chaperone essential for cytochrome c maturation. Science 1998; 281:1197–1200.CrossRefPubMedGoogle Scholar
  14. 14.
    Goldman BS, Gabbert KK, Kranz RG. Use of heme reporters for studies of cytochrome biosynthesis and heme transport. J Bacteriol 1996; 178:6338–6347.PubMedGoogle Scholar
  15. 15.
    Throne-Holst M, Thöny-Meyer L, Hederstedt L. Escherichia coli ccm in-frame deletion mutants can produce periplasmic cytochrome b, but not cytochrome c. FEBS Lett 1997; 410:351–355.CrossRefPubMedGoogle Scholar
  16. 16.
    Myers JM, Myers CR. Role of the tetraheme cytochrome CymA in anaerobic electron transport in cells of Shewanella putrefaciens MR-1 with normal levels of menaquinone. J Bacteriol 2000; 182(1):67–75.CrossRefPubMedGoogle Scholar
  17. 17.
    Myers JM, Myers CR. Role for outer membrane cytochromes OmcA and OmcB of Shewanella putrefaciens MR-1 in reduction of manganese dioxide. Appl Environ Microbiol 2001; 67:260–269.CrossRefPubMedGoogle Scholar
  18. 18.
    Genco CA, Dixon DW. Emerging strategies in microbial haem capture. Mol Microbiol 2001; 39:1–11.CrossRefPubMedGoogle Scholar
  19. 19.
    Stojiljkovic I, Perkins-Balding D. Processing of heme and heme-containing proteins by bacteria. DNA Cell Biol 2002; 21:281–295.CrossRefPubMedGoogle Scholar
  20. 20.
    Wandersman C, Stojiljkovic I. Bacterial heme sources: The role of heme, hemoprotein receptors and hemophores. Curr Opin Microbiol 2000; 3:215–220.CrossRefPubMedGoogle Scholar
  21. 21.
    Braun V, Killmann H. Bacterial solutions to the iron-supply problem. Trends Biochem Sci 1999; 24(3):104–109.CrossRefPubMedGoogle Scholar
  22. 22.
    Letoffe S, Nato F, Goldberg ME et al. Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR. Mol Microbiol 1999; 33:546–555.CrossRefPubMedGoogle Scholar
  23. 23.
    Cope LD, Thomas SE, Hrkal Z et al. Binding of heme-hemopexin complexes by soluble HxuA protein allows utilization of this complexed heme by Haemophilus influenzae. Infect Immun 1998; 66:4511–4516.PubMedGoogle Scholar
  24. 24.
    Arnoux P, Haser R, Izadi N et al. The crystal structure of HasA, a hemophore secreted by Serratia marcescens. Nat Struct Biol 1999; 6:516–520.CrossRefPubMedGoogle Scholar
  25. 25.
    Arnoux P, Haser R, Izadi-Pruneyre N et al. Functional aspects of the heme bound hemophore HasA by structural analysis of various crystal forms. Proteins 2000; 41:202–210.CrossRefPubMedGoogle Scholar
  26. 26.
    Klebba PE, Newton SM. Mechanisms of solute transport through outer membrane porins: Burning down the house. Curr Opin Microbiol 1998; 1:238–247.CrossRefPubMedGoogle Scholar
  27. 27.
    Drazek ES, Hammack CA, Schmitt MP. Corynebacterium diphtheriae genes required for acquisition of iron from haemin and haemoglobin are homologous to ABC haemin transporters. Mol Microbiol 2000; 36:68–84.CrossRefPubMedGoogle Scholar
  28. 28.
    Mazmanian SK, Ton-That H, Su K et al. An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis. Proc Natl Acad Sci USA 2002; 99:2293–2298.CrossRefPubMedGoogle Scholar
  29. 29.
    Mazmanian SK, Skaar EP, Gaspar AH et al. Passage of heme-iron across the envelope of Staphylococcus aureus. Science 2003; 299:906–909.CrossRefPubMedGoogle Scholar
  30. 30.
    Wilks A. The ShuS protein of Shigella dysenteriae is a heme-sequestering protein that also binds DNA. Arch Biochem Biophys 2001; 387:137–142.CrossRefPubMedGoogle Scholar
  31. 31.
    Beckman DL, Trawick DR, Kranz RG. Bacterial cytochromes c biogenesis. Genes Devel 1992; 6:268–283.CrossRefPubMedGoogle Scholar
  32. 32.
    Ramseier TM, Winteler HV, Hennecke H. Discovery and sequence analysis of bacterial genes involved in the biogenesis of c-type cytochromes. J Biol Chem 1991; 266:7793–7803.PubMedGoogle Scholar
  33. 33.
    Goldman BS, Kranz RG. ABC transporters associated with cytochrome c biogenesis. Res Microbiol 2001; 152:323–329.CrossRefPubMedGoogle Scholar
  34. 34.
    Schulz H, Pellicioli E, Thöny-Meyer L. New insights into the role of CcmC, CcmD, and CcmE in the haem delivery pathway during cytochrome c maturation by a complete mutational analysis of the conserved tryptophan-rich motif of CcmC. Mol Microbiol 2000; 37:1379–1388.CrossRefPubMedGoogle Scholar
  35. 35.
    Page MD, Ferguson SJ. Mutational analysis of the Paracoccus denitrificans c-type cytochrome biosynthetic genes ccmABCDG: Disruption of ccmC has distinct effects suggesting a role for CcmC independent of CcmAB. Microbiology 1999; 145:3047–3057.PubMedGoogle Scholar
  36. 36.
    Cook GM, Poole RK. Oxidase and periplasmic cytochrome assembly in Escherichia coli K-12: CydDC and CcmAB are not required for haem-membrane association. Microbiology 2000; 146:527–536.PubMedGoogle Scholar
  37. 37.
    Schulz H, Fabianek RA, Pellicioli et al. Heme transfer to the heme chaperone CcmE during cytochrome c maturation requires the CcmC protein, which may function independently of the ABC-transporter CcmAB. Proc Natl Acad Sci USA 1999; 96:6462–6467.CrossRefPubMedGoogle Scholar
  38. 38.
    Harbin BM, Dailey HA. Orientation of ferrochelatase in bovine liver mitochondria. Biochemistry 1985; 24(2):366–370.CrossRefPubMedGoogle Scholar
  39. 39.
    Soga O, Kinoshita H, Ueda M et al. Evaluation of peroxisomal heme in yeast. J Biochem (Tokyo) 1997; 121:25–28.Google Scholar
  40. 40.
    Lo SC, Aft R, Mueller GC. Role of nonhemoglobin heme accumulation in the terminal differentiation of Friend erythroleukemia cells. Cancer Res 1981; 41:864–870.PubMedGoogle Scholar
  41. 41.
    Zhang L, Guarente L. Heme binds to a short sequence that serves a regulatory function in diverse proteins. EMBO J 1995; 14:313–320.PubMedGoogle Scholar
  42. 42.
    Cornah JE, Roper JM, Pal Singh D et al. Measurement of ferrochelatase activity using a novel assay suggests that plastids are the major site of haem biosynthesis in both photosynthetic and nonphotosynthetic cells of pea (Pisum sativum L.). Biochem J 2002; 362:423–432.CrossRefPubMedGoogle Scholar
  43. 43.
    Shirihai OS, Gregory T, Yu C et al. ABC-me: A novel mitochondrial transporter induced by GATA-1 during erythroid differentiation. EMBO J 2000; 19:2492–2502.CrossRefPubMedGoogle Scholar
  44. 44.
    Müller-Eberhard U, Nikkila H. Transport of tetrapyrroles by proteins. Semin Hematol 1989; 26:86–104.PubMedGoogle Scholar
  45. 45.
    Smith A. Transport of tetrapyrroles: Mechanisms and biological and regulatory consequences. In: Dailey HA, ed. Biosynthesis of heme and chlorophylls. New York: McGraw-Hill, 1990:435–490.Google Scholar
  46. 46.
    Paoli M, Anderson BF, Baker MH et al. Crystal structure of hemopexin reveals a novel high-affinity heme site formed between two beta-propeller domains. Nat Struct Biol 1999; 6:926–931.CrossRefPubMedGoogle Scholar
  47. 47.
    Rose MY, Thompson RA, Light WR et al. Heme transfer between phospholipid membranes and uptake by apohemoglobin. J Biol Chem 1985; 260:6632–6640.PubMedGoogle Scholar
  48. 48.
    Tipping E, Ketterer B, Christodoulides L et al. The interactions of haem with ligandin and aminoazo-dye-binding protein A. Biochem J 1976; 157:461–467.PubMedGoogle Scholar
  49. 49.
    Cannon JB, Kuo FS, Pasternack RF et al. Kinetics of the interaction of hemin liposomes with heme binding proteins. Biochemistry 1984; 23:3715–3721.CrossRefPubMedGoogle Scholar
  50. 50.
    Light IIIrd WR, Olson JS. Transmembrane movement of heme. J Biol Chem 1990; 265:15623–15631.Google Scholar
  51. 51.
    Yoda B, Israels LG. Transfer of heme from mitochondria in rat liver cells. Can J Biochem 1972; 50:633–637.CrossRefPubMedGoogle Scholar
  52. 52.
    Mathews A, Brittain T. Haem disorder in recombinant-and reticulocyte-derived haemoglobins: Evidence for stereoselective haem insertion in eukaryotes. Biochem J 2001; 357:305–311.CrossRefPubMedGoogle Scholar
  53. 53.
    Vasudevan G, McDonald MJ. Spectral demonstration of semihemoglobin formation during CN-hemin incorporation into human apohemoglobins. J Biol Chem 1997; 272:517–524.CrossRefPubMedGoogle Scholar
  54. 54.
    Kihm AJ, Kong Y, Hong W et al. An abundant erythroid protein that stabilizes free alpha-haemoglobin. Nature 2002; 417:758–763.CrossRefPubMedGoogle Scholar
  55. 55.
    Osborne JP, Gennis RB. Sequence analysis of cytochrome bd oxidase suggests a revised topology for subunit I. Biochim Biophys Acta 1999; 1410:32–50.CrossRefPubMedGoogle Scholar
  56. 56.
    Pittman MS, Corker H, Wu G et al. Cysteine is exported from the Escherichia coli cytoplasm by CydDC, an ATP-binding cassette-type transporter required for cytochrome assembly. J Biol Chem 2002; 277:49841–49849.CrossRefPubMedGoogle Scholar
  57. 57.
    Cook GM, Cruz-Ramos H, Moir AJ et al. A novel haem compound accumulated in Escherichia coli overexpressing the cydDC operon, encoding an ABC-type transporter required for cytochrome assembly. Arch Microbiol 2002; 178:358–369.CrossRefPubMedGoogle Scholar
  58. 58.
    Enggist E, Thöny-Meyer L, Güntert P et al. NMR structure of the heme chaperone CcmE reveals a novel functional motif. Structure 2002; 10:1551–1557.CrossRefPubMedGoogle Scholar
  59. 59.
    Arnesano F, Banci L, Barker PD et al. Solution structure and characterization of the heme chaperone CcmE. Biochemistry 2002; 41:13587–13594.CrossRefPubMedGoogle Scholar
  60. 60.
    Daltrop O, Stevens JM, Higham CW et al. The CcmE protein of the c-type cytochrome biogenesis system: Unusual in vitro heme incorporation into apo-CcmE and transfer from holo-CcmE to apocytochrome. Proc Natl Acad Sci USA 2002; 99:9703–9708.CrossRefPubMedGoogle Scholar
  61. 61.
    Ren Q, Thöny-Meyer L. Physical interaction of CcmC with heme and the heme chaperone CcmE during cytochrome c maturation. J Biol Chem 2001; 276:32591–32596.CrossRefPubMedGoogle Scholar
  62. 62.
    Ren Q, Ahuja U, Thöny-Meyer L. A bacterial cytochrome c heme lyase: CcmF forms a complex with the heme chaperone CcmE and CcmH but not with apocytochrome c. J Biol Chem 2002; 277:7657–7663.CrossRefPubMedGoogle Scholar
  63. 63.
    Beckett CS, Lougham JA, Karberg KA et al. Four genes are required for the system II cytochrome c biogenesis pathway in Bordetella pertussis, a unique bacterial model. Mol Microbiol 2000; 38:465–481.CrossRefPubMedGoogle Scholar
  64. 64.
    Hamel PP, Dreyfuss W, Xie Z et al. Essential histidine and tryptophan residues in CcsA, a system II polytopic cytochrome c biogenesis protein. J Biol Chem 2003; 278:2593–2603.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Laboratory of Biomaterials, Empa Swiss Federal Laboratories for MaterialsTesting and ResearchSt. GallenSwitzerland

Personalised recommendations