Archives of Microbiology

, Volume 182, Issue 1, pp 1–6 | Cite as

Lipoprotein trafficking in Escherichia coli

  • Shin-ichiro Narita
  • Shin-ichi Matsuyama
  • Hajime Tokuda


Bacterial lipoproteins comprise a subset of membrane proteins that are covalently modified with lipids at the amino-terminal Cys. Lipoproteins are involved in a wide variety of functions in bacterial envelopes. Escherichia coli has more than 90 species of lipoproteins, most of which are located on the periplasmic surface of the outer membrane, while others are located on that of the inner membrane. In order to elucidate the mechanisms by which outer-membrane-specific lipoproteins are sorted to the outer membrane, biochemical, molecular biological and crystallographic approaches have been taken. Localization of lipoproteins on the outer membrane was found to require a lipoprotein-specific sorting machinery, the Lol system, which is composed of five proteins (LolABCDE). The crystal structures of LolA and LolB, the periplasmic chaperone and outer-membrane receptor for lipoproteins, respectively, were determined. On the basis of the data, we discuss here the mechanism underlying lipoprotein transfer from the inner to the outer membrane through Lol proteins. We also discuss why inner membrane-specific lipoproteins remain on the inner membrane.


Lipoprotein Lol system Outer membrane Sorting signal ABC transporter 



We wish to thank Rika Ishihara for her help in the preparation of this review. The work described here was supported by grants to H. T. from the Ministry of Education, Science, Sports and Culture of Japan.


  1. Braun V, Wu HC (1994) Lipoproteins, structure, function, biosynthesis and model for protein export. In: Ghuysen J-M, Hakenbeck R (eds) New comprehensive biochemistry, vol 27. Bacterial cell wall. Elsevier, Amsterdam, pp 319–341Google Scholar
  2. Chen J, Sharma S, Quiocho FA, Davidson AL (2001) Trapping the transition state of an ATP-binding cassette transporter: evidence for a concerted mechanism of maltose transport. Proc Natl Acad Sci USA 98:1525–1530CrossRefPubMedGoogle Scholar
  3. DeChavigny A, Heacock PN, Dowhan W (1991) Sequence and inactivation of the pss gene of Escherichia coli. Phosphatidylethanolamine may not be essential for cell viability. J Biol Chem 266:5323–5332PubMedGoogle Scholar
  4. Doerrler WT, Ready MC, Raetz CR (2001) An Escherichia coli mutant defective in lipid export. J Biol Chem 276:11461–11464CrossRefPubMedGoogle Scholar
  5. Driessen AJ, Manting EH, van der Does C (2001) The structural basis of protein targeting and translocation in bacteria. Nat Struct Biol 8:492–498CrossRefPubMedGoogle Scholar
  6. Duong F, Eichler J, Price A, Leonard MR, Wickner W (1997) Biogenesis of the gram-negative bacterial envelope. Cell 91:567–573PubMedGoogle Scholar
  7. Economou A (2002) Bacterial secretome: the assembly manual and operating instructions. Mol Membr Biol 19:159–169CrossRefPubMedGoogle Scholar
  8. Fukuda A, Matsuyama S, Hara T, Nakayama J, Nagasawa H, Tokuda H (2002) Aminoacylation of the N-terminal cysteine is essential for Lol-dependent release of lipoproteins from membranes but does not depend on lipoprotein sorting signals. J Biol Chem 277:43512–43518CrossRefPubMedGoogle Scholar
  9. Gennity JM, Inouye M (1991) The protein sequence responsible for lipoprotein membrane localization in Escherichia coli exhibits remarkable specificity. J Biol Chem 266:16458–16464PubMedGoogle Scholar
  10. Hara T, Matsuyama S, Tokuda H (2003) Mechanism underlying the inner membrane retention of E. coli lipoproteins caused by Lol avoidance signals. J Biol Chem 278:40408–40414CrossRefPubMedGoogle Scholar
  11. Hayashi S, Wu HC (1990) Lipoproteins in bacteria. J Bioenerg Biomembr 22:451–471PubMedGoogle Scholar
  12. Masuda K, Matsuyama S, Tokuda H (2002) Elucidation of the function of lipoprotein-sorting signals that determine membrane localization. Proc Natl Acad Sci USA 99:7390–7395CrossRefPubMedGoogle Scholar
  13. Matsuyama S, Tajima T, Tokuda H (1995) A novel periplasmic carrier protein involved in the sorting and transport of Escherichia coli lipoproteins destined for the outer membrane. EMBO J 14:3365–3372PubMedGoogle Scholar
  14. Matsuyama S, Yokota N, Tokuda H (1997) A novel outer membrane lipoprotein, LolB (HemM), involved in the LolA (p20)-dependent localization of lipoproteins to the outer membrane of Escherichia coli. EMBO J 16:6947–6955CrossRefPubMedGoogle Scholar
  15. Miyamoto A, Matsuyama S, Tokuda H (2001) Mutant of LolA, a lipoprotein-specific molecular chaperone of Escherichia coli, defective transfer of lipoprotein to LolB. Biochem Biophys Res Commun 287:1125–1128CrossRefPubMedGoogle Scholar
  16. Miyamoto A, Matsuyama S, Tokuda (2002) Dominant negative mutant of a lipoprotein-specific molecular chaperone, LolA, tightly associates with LolCDE. FEBS Lett 528:193–196CrossRefPubMedGoogle Scholar
  17. Mori H, Ito K (2001) The Sec protein-translocation pathway. Trends Microbiol 9:494–500CrossRefPubMedGoogle Scholar
  18. Muller M, Koch HG, Beck K, Schafer U (2000) Protein traffic in bacteria: multiple routes from the ribosome to and across the membrane. Prog Nucleic Acid Res Mol Biol 66:107–157CrossRefGoogle Scholar
  19. Narita S, Tanaka K, Matsuyama S, Tokuda H (2002) Disruption of lolCDE encoding an ATP-binding-cassette transporter is lethal for Escherichia coli and prevents the release of lipoproteins from the inner membrane. J Bacteriol 184:1417–1422PubMedGoogle Scholar
  20. Narita S, Kanamaru K, Matsuyama S, Tokuda H (2003) A mutation in the membrane subunit of an ABC transporter LolCDE complex causing outer membrane localization of lipoproteins against their inner membrane-specific signals. Mol Microbiol 49:167–177CrossRefPubMedGoogle Scholar
  21. Pugsley AP (1993) The complete general secretory pathway in Gram-negative bacteria. Microbiol Rev 57:50–108PubMedGoogle Scholar
  22. Pugsley AP, d’Enfert C, Reyss I, Kornacker MG (1990) Genetics of extracellular protein secretion by Gram-negative bacteria. Annu Rev Genet 24:67–90CrossRefPubMedGoogle Scholar
  23. Robichon C, Bonhivers M, Pugsley AP (2003) An intramolecular disulphide bond reduces the efficacy of a lipoprotein plasma membrane sorting signal. Mol Microbiol 49:1145–1154CrossRefPubMedGoogle Scholar
  24. Sankaran K, Wu HC (1994) Lipid modification of bacterial prolipoproteins. Transfer of diacylglyceryl moiety from phosphatidylglycerol. J Biol Chem 269:19701–19706PubMedGoogle Scholar
  25. Seydel A, Gounon P, Pugsley AP (1999) Testing the ‘+2 rule’ for lipoprotein sorting in the Escherichia coli cell envelope with a new genetic selection. Mol Microbiol 34:810–821CrossRefPubMedGoogle Scholar
  26. Spurlino JC, Lu G-Y, Quiocho FA (1991) The 2.3-Å resolution structure of the maltose- or maltodextrin-binding protein, a primary receptor of bacterial active transport and chemotaxis. J Biol Chem 266:5202–5219PubMedGoogle Scholar
  27. Tajima T, Yokota N, Matsuyama S, Tokuda H (1998) Genetic analyses of the in vivo function of LolA, a periplasmic chaperone involved in the outer membrane localization of Escherichia coli lipoproteins. FEBS Lett 439:51–54CrossRefPubMedGoogle Scholar
  28. Takeda K, Miyatake H, Yokota N, Matsuyama S, Tokuda H, Miki K (2003) Crystal structures of bacterial lipoprotein localization factors, LolA and LolB. EMBO J 22:3199–3209CrossRefPubMedGoogle Scholar
  29. Tanaka K, Matsuyama S, Tokuda H (2001) Deletion of lolB encoding an outer membrane lipoprotein is lethal for Escherichia coli and causes the accumulation of lipoprotein localization intermediates in the periplasm. J Bacteriol 183:6538–6542CrossRefPubMedGoogle Scholar
  30. Terada M, Kuroda T, Matsuyama S, Tokuda H (2001) Lipoprotein sorting signals evaluated as the LolA-dependent release of lipoproteins from the inner membrane of Escherichia coli. J Biol Chem 276:47690–47694CrossRefPubMedGoogle Scholar
  31. Yakushi T, Yokota N, Matsuyama S, Tokuda H (1998) LolA-dependent release of a lipid-modified protein from the inner membrane of Escherichia coli requires nucleotide triphosphate. J Biol Chem 273:32576–32581CrossRefPubMedGoogle Scholar
  32. Yakushi T, Masuda K, Narita S, Matsuyama S, Tokuda H (2000) A new ABC transporter mediating the detachment of lipid-modified proteins from membranes. Nat Cell Biol 2:212–218PubMedGoogle Scholar
  33. Yamaguchi K, Yu F, Inouye M (1988) A single amino acid determinant of the membrane localization of lipoproteins in E. coli. Cell 53:423–432CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Shin-ichiro Narita
    • 1
  • Shin-ichi Matsuyama
    • 1
    • 2
  • Hajime Tokuda
    • 1
  1. 1.Institute of Molecular and Cellular BiosciencesUniversity of TokyoTokyoJapan
  2. 2.Department of Life ScienceRikkyo UniversityTokyoJapan

Personalised recommendations