Skip to main content

The Leucine\Lrp Regulon

  • Chapter

Abstract

The leucine/Lrp regulon is a recently described global response governed by a transcriptional regulator called the leucine-responsive regulatory protein (Lrp), a small basic protein (pI 9.2) composed of two identical subunits of molecular weight 18 800 daltons.1 Its sequence resembles only one other E. coli protein, AsnC, a positive regulator of asnA (the structural gene of asparagine synthetase A), with which it has 25% amino acid similarity. Cells deficient in Lrp show altered transcription of between 35 and 75 genes,23 increasing the expression of some and decreasing that of others.4–7 At some target promoters the presence of L-leucine in the growth medium modifies Lrp action, as observed with classic regulators, whereas at other LRP-regulated promoters leucine has little or no effect. Several reviews of the regulon have recently appeared.4,6,8,9

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Willins DA, Ryan CW, Platko JV et al. Characterization of Lrp, an Escherichia coli regulatory protein that mediates a global response to leucine. J Biol Chem 1991; 266:10768–74.

    Google Scholar 

  2. Ernsting BR, Atkinson MR, Ninfa AJ et al. Characterization of the regulon controlled by the leucine responsive regulatory protein in Escherichia coli. J Bacteriol 1992; 174:1109–18.

    Google Scholar 

  3. Lin RT, D’Ari R, Newman EB. λplacMu insertions in genes of the leucine regulon: extension of the regulon to genes not regulated by leucine. J Bacteriol 1992; 174:1948–55.

    Google Scholar 

  4. D’Ari R, Lin RT, Newman EB. The leucine-responsive regulatory protein: more than a regulator? Trends Biochem Sci 1993; 18:260–63.

    Article  Google Scholar 

  5. Lin R, D’Ari R, Newman EB. The leucine regulon of Escherichia coli: a mutation in rblA alters expression of leucine-dependent metabolic operons. J Bacteriol 1990; 172:4529–35.

    Google Scholar 

  6. Newman EB, D’Ari R, Lin RT. The leucine-Lrp regulon in E. coli: a global response in search of a raison d’être. 1992 Cell 68:617–19.

    Google Scholar 

  7. Platko JV, Willins DA, Calvo JM. The ilvlH operon of Escherichia coli is positively regulated. J Bacteriol 1990; 172:4563–70.

    Google Scholar 

  8. Calvo JM, Matthews RG. Leucine-responsive regulatory protein- a global regulator of metabolism in Escherichia coli. Microbiol Rev 1994; 58:466–98.

    Google Scholar 

  9. Newman EB, Lin RT. The leucine-responsive reulatory protein, a global regulator of gene expression in E. coli. Annu Rev Microbiol 1995; 49:in press.

    Google Scholar 

  10. Ricca E, Aker DA, Calvo JM. A protein that binds to the regulatory region of the Escherichia coli ilvIH operon. J Bacteriol 1989; 171:1658–64.

    Google Scholar 

  11. Templeton ΒΑ, Savageau MA. Transport of biosynthetic intermediates: regulation of homoserine and threonine uptake in Escherichia coli. J Bacteriol 1974; 120:114–20.

    Google Scholar 

  12. Anderson JJ, Quay SC, and Oxender DL. Mapping of two loci affecting the regulation of branched-chain amino acid transport in Escherichia coli Κ-12. J. Bacteriol 1976; 126:80–90.

    Google Scholar 

  13. Austin EA, Andrews JC, Short SA. Selection, characterization and cloning of oppI, a regulator of the E. coli oligopeptide permease Operon. Abstr Mol Genet Bacteria Phages, abstr. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1989:153.

    Google Scholar 

  14. Braaten BA, Platico JV, van der Woude MW et al. Leucine-responsive regulatory protein controls the expression of both the pap and fan pili operons in Escherichia coli. Proc Natl Acad Sci USA 1992; 89:4250–4.

    Article  Google Scholar 

  15. Andrews JC, Blevins TC, Short SA. Regulation of peptide transport in Escherichia coli: induction of the trp-linked Operon encoding the oligopeptide permease. J Bacteriol 1986; 165:428–33.

    Google Scholar 

  16. Arst Jr HN, Integrator gene in Aspergillus nidulans. Nature 1994; 262:231–4.

    Article  Google Scholar 

  17. Ishizuka H, Hanamura A, Kunimura Τ et al. A lowered concentration of cAMP receptor protein caused by glucose is an important determinant for catabolite repression in Escherichia coli. Mol Microbiol 1994; 6:2489–95.

    Google Scholar 

  18. Lange R, Barth M, Hengge-Aronis R. Complex transcriptional control of the sS-dependent stationary-phase-induced and osmotically regulated osmY (cis-5) gene suggests novel roles for Lrp, cyclic AMP (cAMP) receptor protein-cAMP complex, and integration host factor in the stationary-phase response of Escherichia coli. J Bacteriol 1993; 175:7910–17.

    Google Scholar 

  19. Madhusudhan KT, Lorenz D, Sokatch JR. The bkdR gene of Pseudomonas putida is required for expression of the bkd Operon and encodes a protein related to Lrp of Escherichia coli. J Bacteriol 1993; 175:3934–40.

    Google Scholar 

  20. Pizer LI. Glycine synthesis and metabolism in Escherichia coli. J Bacteriol. 1967; 89:1145–50.

    Google Scholar 

  21. Su H, Lang BF, Newman EB. L-Serine degradation in Escherichia coli Κ-12. Cloning and sequencing of the sdaA gene. J Bacteriol 1989; 171:5095–102.

    Google Scholar 

  22. Levinthal M, Lejeune P, Danchin A. The H-NS protein modulates the activation of the ilvlH Operon of Escherichia coli K12 by Lrp, the leucine regulatory protein. Mol Gen Genet 1994; 242:736–43.

    Article  Google Scholar 

  23. Platko JV, Calvo JM. Mutations affecting the ability of Escherichia coli Lrp to bind DNA, activate transcription, or respond to leucine. J Bacteriol 1993; 175:1110–17.

    Google Scholar 

  24. Wang Q, Calvo JM. Lrp, a major regulatory protein in Escherichia coli, bends DNA and can organize the assembly of a higher-order nucleopro-tein structure. EMBO J 1993; 12:2495–501.

    Google Scholar 

  25. Wang Q, Wu J, Friedberg D et al. Regulation of the Escherichia coli lrp gene. J Bacteriol 1994; 176:1831–9.

    Google Scholar 

  26. Ernsting BR, Denninger JW, Blumenthal RM et al. Regulation of the gltBDF Operon of Escherichia coli: how is a leucine-insensitive Operon regulated by the leucine-responsive regulatory protein? J Bacteriol 1993; 175:7160–9.

    Google Scholar 

  27. Ambartsoumian G, D’Ari R, Lin RT et al. Altered amino acid metabolism in lrp mutants of Escherichia coli and their derivatives. Microbiol 1994; 140:1737–44.

    Article  Google Scholar 

  28. Tchetina E, Newman EB. Identification of Lrp-regulated genes by inverse PCR and sequencing: an insert in E. coli malF is regulated by leucine-responsive regulatory protein. J Bacteriol 1995; (in press)

    Google Scholar 

  29. Su H, Moniakis J, Newman EB. Use of gene fusions of the structural gene sdaA to purify L-serine deaminase 1 from Escherichia coli Κ-12. Eur J biochem 1993; 211:521–7.

    Article  Google Scholar 

  30. Newman EB, Batist G, Fraser J et al. The use of glycine as nitrogen source by Escherichia coli K-12. Biochim Biophys Acta 1976; 421:97–105.

    Article  Google Scholar 

  31. Newman EB, Miller B, Kapoor V. Biosynthesis of single-carbon units in Escherichia coli K-12. Biochim Biophys Acta 1974; 338:529–39.

    Article  Google Scholar 

  32. Friedberg D., Platico JV, Tyler Β, Calvo JM. The amino acid sequence of Lrp is highly conserved in four enteric microorganisms. J Bacteriol 1995; 177:(in press).

    Google Scholar 

  33. Braaten BA, Blyn LB, Skinner BS et al. 1991. Evidence for a methyla-tion-blocking factor (mbf) locus involved in pap pilus expression and phase variation in Escherichia coli. J Bacteriol 1991; 173:1789–1800.

    Google Scholar 

  34. Andrews JC, Short SA. opp-lac Operon fusions and transcriptional regulation of the Escherichia coli trp-linked oligopeptide permease. J Bacteriol 1986; 165:434–42.

    Google Scholar 

  35. Smith DW, Stine WB, Svitil AV et al. Escherichia coli cells lacking methylation-blocking factor (leucine-responsive regulatory protein) have precise timing of initiation of DNA replication in the cell cycle. J Bacteriol 1992; 174:3078–82.

    Google Scholar 

  36. Drlica K, Rouviere-Yaniv J. Histonelike proteins of bacteria. Microbiol Rev 1987; 51:301–19.

    Google Scholar 

  37. Rouviere-Yaniv J, Yaniv M, Germond JE. Ε. coli DNA binding protein HU forms nucleosome-like structure with circular double-stranded DNA. Cell 1979; 17:265–74.

    Article  Google Scholar 

  38. Freundlich M, Ramani Ν, Mathew Ε et al. The role of integration host factor in gene expression in Escherichia coli. Mol Microbiol 1992; 6:2557–63.

    Article  Google Scholar 

  39. Schultz SC, Shields GC, Steitz TA. Crystal structure of a CAP-DNA complex: the DNA is bent by 90=B0. Science 1991; 253:1001–7.

    Article  Google Scholar 

  40. Haughn GW, Squires CH, De Felice M et al. Unusual organization of the ilvIH promoter in Escherichia coli. J Bacteriol 1985; 163:186–98.

    Google Scholar 

  41. Willins DA, Calvo JM. In vitro transcription from the Escherichia coli ilvIH promoter. J Bacteriol 1992; 174:7648–55.

    Google Scholar 

  42. Wang Q, Calvo JM. Lrp, a global regulatory protein of Escherichia coli, binds co-operatively to multiple sites and activates transcription of ilvIH. J Mol Biol 1993; 229:306–18.

    Article  Google Scholar 

  43. Wang Q, Sacco M, Ricca Ε et al. Organization of Lrp-binding sites upstream of ilvIH in Salmonella typhimurium. Mol Microbiol 1993; 7:883–91.

    Article  Google Scholar 

  44. Sacco M, Ricca E, Marasco R et al. A stereospecific alignment between the promoter and the cis-acting sequence is required for Lrp-dependent activation of ilvIH transcription in Escherichia coli. FEMS Microbiol Lett 1993; 107:331–6.

    Article  Google Scholar 

  45. Van der Woude MW, Braaten BA, Low DA. Evidence for global regulatory control of pilus expression in Escherichia coli by Lrp and DNA me-thylation: model building based on analysis of pap. Mol Microbiol 1992; 6:2429–35.

    Article  Google Scholar 

  46. Hale WB, van der Woude MW, Low DA. Analysis of nonmethylated GATC sites in the Escherichia coli chromosome and identification of sites that are differentially methylated in response to environmental stimuli. J Bacteriol 1994; 176:3438–41.

    Google Scholar 

  47. Lin R, Characterization of the leucine/Lrp regulon in Escherichia coli K-12. Thesis, Concordia University, Montreal, Quebec, Canada, 1992.

    Google Scholar 

  48. Ravnikar PD, Somerville RL. Genetic characterization of a highly efficient alternative pathway of serine biosynthesis in Escherichia coli. J Bacteriol 1987; 169:2611–17.

    Google Scholar 

  49. Wilson RL, Stauffer GV. DNA sequence and characterization of gcvA, a lysR family regulatory protein for the Escherichia coli glycine cleavage enzyme system. J Bacteriol. 1994; 176:2862–8.

    Google Scholar 

  50. Lin R, Ernsting B, Hirshfield IN et al. The lrp gene product regulates expression of lysU in Escherichia coli Κ-12. J Bacteriol 1992; 174:2779–84.

    Google Scholar 

  51. Rex JH, Aronson BD, Somerville RL. The tdh and serA operons of Escherichia coli: mutational analysis of the regulatory elements of leucine-responsive genes. J Bacteriol 1991; 173:5944–53.

    Google Scholar 

  52. Perez-Martin J, Rojo F, de Lorenzo V. Promoters responsive to DNA bending: a common theme in procaryotic gene expression. Microbiol Rev 1994; 58:268–90.

    Google Scholar 

  53. Shao ZQ, Newman EB. Sequencing and characterization of the sdaB gene from Escherichia coli K-12. Eur J Biochem 1993; 212:777–84.

    Article  Google Scholar 

  54. Siegele DA, Kolter R. Life after log. J Bacteriol 1992; 174:345–8.

    Google Scholar 

  55. Ferrario M, Ernsting BR, Borst DW et al. The leucine-responsive regulatory protein of Escherichia coli negatively regulates transcription of ompC and micF and positively regulates translation of ompF. J Bacteriol 1995; 177:103–13.

    Google Scholar 

  56. Raina S, Missiakas D, Baird L et al. Identification and transcriptional analysis of the Escherichia coli htrE Operon which is homologous to pap and related pilin operons. J Bacteriol 1993; 175:5009–21.

    Google Scholar 

  57. Gaily DL, Bogan JA, Eisenstein BI et al. Environmental regulation of the fim switch controlling type 1 fimbrial phase variation in Escherichia coli K-12: effects of temperature and media. J Bacteriol 1993; 175:6186–93.

    Google Scholar 

  58. Isenberg S, Newman EB. Studies on L-serine deaminase in Escherichia coli K-12. J Bacteriol 1974; 118:53–8.

    Google Scholar 

  59. Leveque F, Gazeau M, Fromant M et al. Control of Escherichia coli lysyl-tRNA synthetase expression by anaerobiosis. J Bacteriol 1991; 173:7903–10.

    Google Scholar 

  60. Nakamura Y, Ito R. Control and function of lysyl-tRNA synthetases: diversity and co-ordination. Mol Microbiol 1993; 10:225–31.

    Article  Google Scholar 

  61. Jamieson DJ, Higgins CF. Anaerobic and leucine-dependent expression of a peptide transport gene in Salmonella typhimurium. J Bacteriol 1984; 160:131–6.

    Google Scholar 

  62. Kawaji H, Mizuno T, Mizushima S. Influence of molecular size and os-molarity of sugars and dextrans on the synthesis of outer membrane proteins 0–8 and 0–9 of Escherichia coli K-12. J Bacteriol 1979; 140:843–7.

    Google Scholar 

  63. Nystrom T, Neidhardt FC. Cloning, mapping and nucleotide sequencing of a gene encoding a universal stress protein in Escherichia coli. Mol Microbiol 1992; 6:3187–98.

    Article  Google Scholar 

  64. Guardaiola J, De Felice M, Klopotowski T et al. Multiplicity of isoleu-cine, leucine, and valine transport systems in Escherichia coli K-12. J Bacteriol 1974; 117:382–92.

    Google Scholar 

  65. Anderson JJ, Oxender DL. Escherichia coli transport mutants lacking binding protein and other components of the branched-chain amino acid transport systems. J Bacteriol 1977; 130:384–92.

    Google Scholar 

  66. Bedouelle H, Schmeissner E, Hofnung M et al. Promoters of the malEFG and malK-lamB operons in Escherichia coli K12. J Mol Biol 1982; 161:519–31.

    Article  Google Scholar 

  67. Ito K, Kawakami K, Nakamura Y. Multiple control of Escherichia coli lysyl-tRNA synthetase expression involves a transcriptional repressor and a translational enhancer element. Proc Natl Acad Sci USA 1993 90:302–6.

    Article  Google Scholar 

  68. Bilge SS, Apostol Jr JM, Fullner KJ et al. Transcriptional organization of the F1845 fimbrial adhesin determinant of Escherichia coli. Mol Microbiol 1993; 7:993–1006.

    Article  Google Scholar 

  69. Blomfield IC, Calie PJ, Eberhardt KJ et al. Lrp stimulates phase variation of type 1 fimbriation in Escherichia coli K-12. J Bacteriol 1993; 175:27–36.

    Google Scholar 

  70. Lawther RP, Calhoun DH, Adams CW et al. Molecular basis of valine resistance in Escherichia coli Κ-12. Proc Natl Acad Sci USA 1981; 78:922–5.

    Article  Google Scholar 

  71. Landick R, Anderson JJ, Mayo MM et al. Regulation of high-affinity leucine transport in Escherichia coli. J Supramol Struct 1980; 14:527–37.

    Article  Google Scholar 

  72. Gerolimatos B, Hanson RL. Repression of Escherichia coli pyridine nucleotide transhydrogenase by leucine. J Bacteriol 1978; 134:394–400.

    Google Scholar 

  73. Nou X, Skinner B, Braaten B. et al. Regulation of pyelonephritis-associated pili phase-variation in Escherichia coli: binding of the Papl and the Lrp regulatory proteins is controlled by DNA methylation. Mol Microbiol 1993; 7:545–53.

    Article  Google Scholar 

  74. Quay SC, Kline EL, Oxender DL. Role of leucyl-tRNA synthetase in regulation of branched-chain amino-acid transport. Proc Natl Acad Sci USA 1975; 72:3921–4.

    Article  Google Scholar 

  75. Shao ZQ, Lin RT, Newman EB. Sequencing and characterization of the sdaC gene and identification of the sdaCB Operon in E. coli Κ-12. Eur J Biochem 1994; 222:901–7.

    Article  Google Scholar 

  76. Van der Woude MW, Low DA. Leucine-responsive regulatory protein and deoxyadenosine methylase control the phase variation and expression of the sfa and daa pili Operons in Escherichia coli. Mol Microbiol 1994; 11:605–18.

    Article  Google Scholar 

  77. Gazeau M, Delort F, Dessen Ρ et al. Escherichia coli leucine-responsive regulatory protein (Lrp) controls lysyl-tRNA synthetase expression. FEBS 1992; 300:254–8.

    Article  Google Scholar 

  78. Haney SA, Plakto JV, Oxender DL et al. Lrp, a leucine-responsive protein, regulates branched-chain amino acid transport genes in Escherichia coli. J Bacteriol 1992; 174:108–15.

    Google Scholar 

  79. Penrose WR, Nichoalds GE, Piperno JR et al. Purification and properties of a leucine-binding protein from Escherichia coli. J Biol Chem 1968; 243:5921–8.

    Google Scholar 

  80. Huisman TT, Bakker D, Klaasen P et al. Leucine-responsive regulatory protein, IS1 insertions, and the negative regulator FaeA control the expression of the fae (K88) Operon in Escherichia coli. Mol Microbiol 1994; 11:525–36.

    Article  Google Scholar 

  81. Bachmann BJ. Linkage map of Escherichia coli Κ-12, ed 8. Microbiol Rev 1990; 54:130–197.

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 1996 R.G. Landes Company

About this chapter

Cite this chapter

Newman, E.B., Lin, R. (1996). The Leucine\Lrp Regulon. In: Regulation of Gene Expression in Escherichia coli . Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-8601-8_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-8601-8_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-8603-2

  • Online ISBN: 978-1-4684-8601-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics