Abstract
The Escherichia coli Leucine-responsive regulatory protein (Lrp) is a nucleoid-associated protein involved in the transcriptional regulation of 10% of all E. coli genes. The structural and biochemical properties of Lrp suggest roles in both the organization of the bacterial chromosome as well as transcriptional regulation. Lrp adopts higher order oligomerization states and shows low sequence specificity, similar to other nucleoid-associated proteins. However, Lrp transcriptionally regulates several E. coli genes, including those involved in metabolic pathways and those involved in virulence. As its name suggests, leucine affects the ability of Lrp to bind certain sequences and regulate certain genes yet many Lrp-regulated genes are not affected by the presence of leucine.
Lrp homologs are found in both Gram-positive and Gram-negative bacteria and among archaea. Crystal structures of E. coli Lrp and various homologs have revealed an octameric structure with conserved motifs in the N and C termini. The role of Lrp in transcription is influenced by such factors as nutrient availability, leucine, interactions with other proteins, and competition with other regulatory proteins for binding specific sequences. Various cellular conditions like nutrient depletion regulate the concentrations of Lrp in the cell which affects the oligomeric state of the protein, influencing its ability to bind to certain sequences.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Azam TA, Ishihama A (1999) Twelve species of the nucleoid-associated protein from Escherichia coli. Sequence recognition specificity and DNA binding affinity. J Biol Chem 274:33105-33113
Azam TA, Iwata A, Nishimura A, Ueda S, Ishihama A (1999) Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid. J Bacteriol 181:6361-6370
Beloin C, Ayora S, Exley R, Hirschbein L, Ogasawara N, Kasahara Y, Alonso JC, Le Hegarat F (1997) Characterization of an lrp-like (lrpC) gene from Bacillus subtilis. Mol Gen Genet 256:63-71
Beloin C, Exley R, Mahe A, Zouine M, Cubasch S, Le Hegarat F (2000) Characterization of LrpC DNA-binding properties and regulation of Bacillus subtilis lrpC gene expression. J Bacteriol 182:4414-4424
Beloin C, Jeusset J, Revet B, Mirambeau G, Le Hegarat F, Le Cam E (2003) Contribution of DNA conformation and topology in right-handed DNA wrapping by the Bacillus subtilis LrpC protein. J Biol Chem 278:5333-5342
Blyn LB, Braaten BA, Low DA (1990) Regulation of pap pilin phase variation by a mechanism involving differential dam methylation states. EMBO J 9:4045-4054
Braaten BA, Platko JV, van der Woude MW, Simons BH, De Graaf FK, Calvo JM, Low DA (1992) Leucine-responsive regulatory protein controls the expression of both the pap and fan pili operons in Escherichia coli. Proc Natl Acad Sci USA 89:4250-4254
Brinkman AB, Bell SD, Lebbink RJ, de Vos WM, van der Oost J (2002) The Sulfolobus solfataricus Lrp-like protein LysM regulates lysine biosynthesis in response to lysine availability. J Biol Chem 277:29537-29549
Calvo JM, Matthews RG (1994) The leucine-responsive regulatory protein, a global regulator of metabolism in Escherichia coli. Microbiol Rev 58:466-490
Chen S, Calvo JM (2002) Leucine-induced dissociation of Escherichia coli Lrp hexadecamers to octamers. J Mol Biol 318:1031-1042
Chen S, Hao Z, Bieniek E, Calvo JM (2001a) Modulation of Lrp action in Escherichia coli by leucine: effects on non-specific binding of Lrp to DNA. J Mol Biol 314:1067-1075
Chen S, Rosner MH, Calvo JM (2001b) Leucine-regulated self-association of leucine-responsive regulatory protein (Lrp) from Escherichia coli. J Mol Biol 312:625-635
Chen S, Iannolo M, Calvo JM (2005) Cooperative binding of the leucine-responsive regulatory protein (Lrp) to DNA. J Mol Biol 345:251-264
Cho K, Winans SC (1996) The putA gene of Agrobacterium tumefaciens is transcriptionally activated in response to proline by an Lrp-like protein and is not autoregulated. Mol Microbiol 22:1025-1033
Cui Y, Wang Q, Stormo GD, Calvo JM (1995) A consensus sequence for binding of Lrp to DNA. J Bacteriol 177:4872-4880
Cui Y, Midkiff MA, Wang Q, Calvo JM (1996) The leucine-responsive regulatory protein (Lrp) from Escherichia coli. Stoichiometry and minimal requirements for binding to DNA. J Biol Chem 271:6611-6617
D’Ari R, Lin RT, Newman EB (1993) The leucine-responsive regulatory protein: more than a regulator? Trends Biochem Sci 18:260-263
De Felice M, Lago CT, Squires CH, Calvo JM (1982) Acetohydroxy acid synthase isoenzymes of Escherichia coli K12 and Salmonella typhimurium. Ann Microbiol (Paris) 133:251-256
de los Rios S, Perona JJ (2007) Structure of the Escherichia coli leucine-responsive regulatory protein Lrp reveals a novel octameric assembly. J Mol Biol 366:1589-1602
De Wind N, de Jong M, Meijer M, Stuitje AR (1985) Site-directed mutagenesis of the Escherichia coli chromosome near oriC: identification and characterization of asnC, a regulatory element in E. coli asparagine metabolism. Nucleic Acids Res 13:8797-8811
Ettema TJ, Brinkman AB, Tani TH, Rafferty JB, van der Oost J (2002) A novel ligand-binding domain involved in regulation of amino acid metabolism in prokaryotes. J Biol Chem 277:37464-37468
Forsman K, Goransson M, Uhlin BE (1989) Autoregulation and multiple DNA interactions by a transcriptional regulatory protein in E. coli pili biogenesis. EMBO J 8:1271-1277
Friedberg D, Platko JV, Tyler B, Calvo JM (1995) The amino acid sequence of Lrp is highly conserved in four enteric microorganisms. J Bacteriol 177:1624-1626
Friedberg D, Midkiff M, Calvo JM (2001) Global versus local regulatory roles for Lrp-related proteins: Haemophilus influenzae as a case study. J Bacteriol 183:4004-4011
Gazeau M, Delort F, Fromant M, Dessen P, Blanquet S, Plateau P (1994) Structure-function relationship of the Lrp-binding region upstream of lysU in Escherichia coli. J Mol Biol 241:378-389
Hernday A, Krabbe M, Braaten B, Low D (2002) Self-perpetuating epigenetic pili switches in bacteria. Proc Natl Acad Sci USA 99(Suppl 4):16470-16476
Hernday AD, Braaten BA, Low DA (2003) The mechanism by which DNA adenine methylase and PapI activate the pap epigenetic switch. Mol Cell 12:947-957
Hernday AD, Braaten BA, Broitman-Maduro G, Engelberts P, Low DA (2004) Regulation of the pap epigenetic switch by CpxAR: phosphorylated CpxR inhibits transition to the phase ON state by competition with Lrp. Mol Cell 16:537-547
Jafri S, Evoy S, Cho K, Craighead HG, Winans SC (1999) A Lrp-type transcriptional regulator from Agrobacterium tumefaciens condenses more than 100 nucleotides of DNA into globular nucleoprotein complexes. J Mol Biol 288:811-824
Jafri S, Chen S, Calvo JM (2002) ilvIH operon expression in Esherichia coli requires Lrp binding to two distinct regions of DNA. J Bacteriol 184:5293-5300
Johnson JR (1991) Virulence factors in Escherichia coli urinary tract infection. Clin Microbiol Rev 4:80-128
Koike H, Ishijima SA, Clowney L, Suzuki M (2004) The archaeal feast/famine regulatory protein: potential roles of its assembly forms for regulating transcription. Proc Natl Acad Sci USA 101:2840-2845
Kolling R, Lother H (1985) AsnC: an autogenously regulated activator of asparagine synthetase. A transcription in Escherichia coli. J Bacteriol 164:310-315
Landgraf JR, Wu J, Calvo JM (1996) Effects of nutrition and growth rate on Lrp levels in Escherichia coli. J Bacteriol 178:6930-6936
Leonard PM, Smits SH, Sedelnikova SE, Brinkman AB, de Vos WM, van der Oost J, Rice DW, Rafferty JB (2001) Crystal structure of the Lrp like transcriptional regulator from the archaeon Pyrococcus furiosus. EMBO J 20:990-997
Levinthal M, Lejeune P, Danchin A (1994) The H-NS protein modulates the activation of the ilvIH operon of Escherichia coli K12 by Lrp, the leucine regulatory protein. Mol Gen Genet 242:736-743
Luijsterburg MS, Noom MC, Wuite GJ, Dame RT (2006) The architectural role of nucleoid-associated proteins in the organization of bacterial chromatin: a molecular perspective. J Struct Biol 156:262-272
Madhusudhan KT, Huang N, Braswell EH, Sokatch JR (1997) Binding of L-branched-chain amino acids causes a conformation change in BkdR. J Bacteriol 179:276-279
McFarland KA, Lucchini S, Hinton JCD, Dorman CJ (2008) The leucine-responsive regulatory protein, Lrp, activates transcription of the fim operon in Salmonella enterica serovar typhimurium via the fimZ regulatory gene. J Bacteriol 190:602-612
Newman EB, Lin R (1995) Leucine-responsive regulatory protein: a global regulator of gene expression in E. coli. Annu Rev Microbiol 49:747-775
Nou X, Braaten B, Kaltenbach L, Low DA (1995) Differential binding of Lrp to two sets of pap DNA binding sites mediated by PapI regulates Pap phase variation in Escherichia coli. EMBO J 14:5785-5797
Peterson SN, Dahlquist FD, Reich NO (2007) The role of high affinity non-specific DNA binding by Lrp in transcriptional regulation and DNA organization. J Mol Biol 369:1307-1317
Platko JV, Calvo JM (1993) Mutations affecting the ability of Escherichia coli Lrp to bind DNA, activate transcription, or respond to leucine. J Bacteriol 175:1110-1117
Pul U, Wurm R, Lux B, Meltzer M, Menzel A, Wagner R (2005) Lrp and H-NS - cooperative partners for transcription regulation at Escherichia coli rRNA promoters. Mol Microbiol 58:864-876
Ricca E, Aker D, Calvo JM (1989) A protein that binds to the regulatory region of the Escherichia coli ilvIH operon. J Bacteriol 171:1658-1664
Tani TH, Khodursky A, Blumenthal RM, Brown PO, Matthews RG (2002) Adaptation to famine: a family of stationary-phase genes revealed by microarray analysis. Proc Natl Acad Sci USA 99:13471-13476
Tapias A, Lopez G, Ayora S (2000) Bacillus subtilis LrpC is a sequence-independent DNA-binding and DNA-bending protein which bridges DNA. Nucleic Acids Res 28:552-559
Thaw P, Sedelnikova SE, Muranova T, Wiese S, Ayora S, Alonso JC, Brinkman AB, Akerboom J, van der Oost J, Rafferty JB (2006) Structural insight into gene transcriptional regulation and effector binding by the Lrp/AsnC family. Nucleic Acids Res 34:1439-1449
Wang Q, Calvo JM (1993a) Lrp, a global regulatory protein of Escherichia coli, binds co-operatively to multiple sites and activates transcription of ilvIH. J Mol Biol 229:306-318
Wang Q, Calvo JM (1993b) Lrp, a major regulatory protein in Escherichia coli, bends DNA and can organize the assembly of a higher order nucleoprotein structure. EMBO J 12:2495-2501
Weyand NJ, Braaten BA, van der Woude M, Tucker J, Low DA (2001) The essential role of the promoter-proximal subunit of CAP in pap phase variation: Lrp- and helical phase-dependent activation of papBA transcription by CAP from −215. Mol Microbiol 39:1504-1522
Wiese DE, Ernsting BR, Blumenthal RM, Matthews RG (1997) A nucleoprotein activation complex between the leucine-responsive regulatory protein and DNA upstream of the gltBDF operon in Escherichia coli. J Mol Biol 270:152-168
Willins DA, Ryan CW, Platko JV, Calvo JM (1991) Characterization of Lrp, and Escherichia coli regulatory protein that mediates a global response to leucine. J Biol Chem 266:10768-10774
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Peterson, S.N., Reich, N.O. (2010). LRP: A Nucleoid-Associated Protein with Gene Regulatory Functions. In: Dame, R.T., Dorman, C.J. (eds) Bacterial Chromatin. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3473-1_15
Download citation
DOI: https://doi.org/10.1007/978-90-481-3473-1_15
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-3472-4
Online ISBN: 978-90-481-3473-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)