2cg4 Citations

Structural insight into gene transcriptional regulation and effector binding by the Lrp/AsnC family.

Abstract

The Lrp/AsnC family of transcriptional regulatory proteins is found in both archaea and bacteria. Members of the family influence cellular metabolism in both a global (Lrp) and specific (AsnC) manner, often in response to exogenous amino acid effectors. In the present study we have determined both the first bacterial and the highest resolution structures for members of the family. Escherichia coli AsnC is a specific gene regulator whose activity is triggered by asparagine binding. Bacillus subtilis LrpC is a global regulator involved in chromosome condensation. Our AsnC-asparagine structure is the first for a regulator-effector complex and is revealed as an octameric disc. Key ligand recognition residues are identified together with a route for ligand access. The LrpC structure reveals a stable octamer supportive of a topological role in dynamic DNA packaging. The structures yield significant clues to the functionality of Lrp/AsnC-type regulators with respect to ligand binding and oligomerization states as well as to their role in specific and global DNA regulation.

Articles - 2cg4 mentioned but not cited (4)

  1. Structural insight into gene transcriptional regulation and effector binding by the Lrp/AsnC family. Thaw P, Sedelnikova SE, Muranova T, Wiese S, Ayora S, Alonso JC, Brinkman AB, Akerboom J, van der Oost J, Rafferty JB. Nucleic Acids Res 34 1439-1449 (2006)
  2. Crystal structure of glutamine receptor protein from Sulfolobus tokodaii strain 7 in complex with its effector L-glutamine: implications of effector binding in molecular association and DNA binding. Kumarevel T, Nakano N, Ponnuraj K, Gopinath SC, Sakamoto K, Shinkai A, Kumar PK, Yokoyama S. Nucleic Acids Res 36 4808-4820 (2008)
  3. Crystal structures of TM0549 and NE1324--two orthologs of E. coli AHAS isozyme III small regulatory subunit. Petkowski JJ, Chruszcz M, Zimmerman MD, Zheng H, Skarina T, Onopriyenko O, Cymborowski MT, Koclega KD, Savchenko A, Edwards A, Minor W. Protein Sci 16 1360-1367 (2007)
  4. The structure, function and properties of sirohaem decarboxylase--an enzyme with structural homology to a transcription factor family that is part of the alternative haem biosynthesis pathway. Palmer DJ, Schroeder S, Lawrence AD, Deery E, Lobo SA, Saraiva LM, McLean KJ, Munro AW, Ferguson SJ, Pickersgill RW, Brown DG, Warren MJ. Mol Microbiol 93 247-261 (2014)


Reviews citing this publication (6)

  1. Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Dillon SC, Dorman CJ. Nat Rev Microbiol 8 185-195 (2010)
  2. The major architects of chromatin: architectural proteins in bacteria, archaea and eukaryotes. Luijsterburg MS, White MF, van Driel R, Dame RT. Crit Rev Biochem Mol Biol 43 393-418 (2008)
  3. Early steps of double-strand break repair in Bacillus subtilis. Alonso JC, Cardenas PP, Sanchez H, Hejna J, Suzuki Y, Takeyasu K. DNA Repair (Amst) 12 162-176 (2013)
  4. Regulatory and pathogenesis roles of Mycobacterium Lrp/AsnC family transcriptional factors. Deng W, Wang H, Xie J. J Cell Biochem 112 2655-2662 (2011)
  5. Role of Proline in Pathogen and Host Interactions. Christgen SL, Becker DF. Antioxid Redox Signal 30 683-709 (2019)
  6. Alanine dehydrogenases in mycobacteria. Jeong JA, Oh JI. J Microbiol 57 81-92 (2019)

Articles citing this publication (54)

  1. A blueprint of ectoine metabolism from the genome of the industrial producer Halomonas elongata DSM 2581 T. Schwibbert K, Marin-Sanguino A, Bagyan I, Heidrich G, Lentzen G, Seitz H, Rampp M, Schuster SC, Klenk HP, Pfeiffer F, Oesterhelt D, Kunte HJ. Environ Microbiol 13 1973-1994 (2011)
  2. Dynamics of genomic-library enrichment and identification of solvent tolerance genes for Clostridium acetobutylicum. Borden JR, Papoutsakis ET. Appl Environ Microbiol 73 3061-3068 (2007)
  3. A central metabolic circuit controlled by QseC in pathogenic Escherichia coli. Hadjifrangiskou M, Kostakioti M, Chen SL, Henderson JP, Greene SE, Hultgren SJ. Mol Microbiol 80 1516-1529 (2011)
  4. Structure of the Escherichia coli leucine-responsive regulatory protein Lrp reveals a novel octameric assembly. de los Rios S, Perona JJ. J Mol Biol 366 1589-1602 (2007)
  5. Proteins evolve on the edge of supramolecular self-assembly. Garcia-Seisdedos H, Empereur-Mot C, Elad N, Levy ED. Nature 548 244-247 (2017)
  6. Crystal structure of the IrrE protein, a central regulator of DNA damage repair in deinococcaceae. Vujicić-Zagar A, Dulermo R, Le Gorrec M, Vannier F, Servant P, Sommer S, de Groot A, Serre L. J Mol Biol 386 704-716 (2009)
  7. Ss-LrpB, a transcriptional regulator from Sulfolobus solfataricus, regulates a gene cluster with a pyruvate ferredoxin oxidoreductase-encoding operon and permease genes. Peeters E, Albers SV, Vassart A, Driessen AJ, Charlier D. Mol Microbiol 71 972-988 (2009)
  8. Lrp of Corynebacterium glutamicum controls expression of the brnFE operon encoding the export system for L-methionine and branched-chain amino acids. Lange C, Mustafi N, Frunzke J, Kennerknecht N, Wessel M, Bott M, Wendisch VF. J Biotechnol 158 231-241 (2012)
  9. MarR-like transcriptional regulator involved in detoxification of aromatic compounds in Sulfolobus solfataricus. Fiorentino G, Ronca R, Cannio R, Rossi M, Bartolucci S. J Bacteriol 189 7351-7360 (2007)
  10. The role of LRP and H-NS in transcription regulation: involvement of synergism, allostery and macromolecular crowding. Pul U, Wurm R, Wagner R. J Mol Biol 366 900-915 (2007)
  11. The role of high affinity non-specific DNA binding by Lrp in transcriptional regulation and DNA organization. Peterson SN, Dahlquist FW, Reich NO. J Mol Biol 369 1307-1317 (2007)
  12. Comparative genomic structures of Mycobacterium CRISPR-Cas. He L, Fan X, Xie J. J Cell Biochem 113 2464-2473 (2012)
  13. Limited functional conservation of a global regulator among related bacterial genera: Lrp in Escherichia, Proteus and Vibrio. Lintner RE, Mishra PK, Srivastava P, Martinez-Vaz BM, Khodursky AB, Blumenthal RM. BMC Microbiol 8 60 (2008)
  14. A structural code for discriminating between transcription signals revealed by the feast/famine regulatory protein DM1 in complex with ligands. Okamura H, Yokoyama K, Koike H, Yamada M, Shimowasa A, Kabasawa M, Kawashima T, Suzuki M. Structure 15 1325-1338 (2007)
  15. Mechanistic insights from the crystal structures of a feast/famine regulatory protein from Mycobacterium tuberculosis H37Rv. Shrivastava T, Ramachandran R. Nucleic Acids Res 35 7324-7335 (2007)
  16. The tyrosine degradation gene hppD is transcriptionally activated by HpdA and repressed by HpdR in Streptomyces coelicolor, while hpdA is negatively autoregulated and repressed by HpdR. Yang H, Wang L, Xie Z, Tian Y, Liu G, Tan H. Mol Microbiol 65 1064-1077 (2007)
  17. Analysis of the DNA-binding sequence specificity of the archaeal transcriptional regulator Ss-LrpB from Sulfolobus solfataricus by systematic mutagenesis and high resolution contact probing. Peeters E, Wartel C, Maes D, Charlier D. Nucleic Acids Res 35 623-633 (2007)
  18. Crystal structure of the archaeal heat shock regulator from Pyrococcus furiosus: a molecular chimera representing eukaryal and bacterial features. Liu W, Vierke G, Wenke AK, Thomm M, Ladenstein R. J Mol Biol 369 474-488 (2007)
  19. Expanded target and cofactor repertoire for the transcriptional activator LysM from Sulfolobus. Song N, Nguyen Duc T, van Oeffelen L, Muyldermans S, Peeters E, Charlier D. Nucleic Acids Res 41 2932-2949 (2013)
  20. Interactions between closely related bacterial strains are revealed by deep transcriptome sequencing. González-Torres P, Pryszcz LP, Santos F, Martínez-García M, Gabaldón T, Antón J. Appl Environ Microbiol 81 8445-8456 (2015)
  21. Sa-Lrp from Sulfolobus acidocaldarius is a versatile, glutamine-responsive, and architectural transcriptional regulator. Vassart A, Van Wolferen M, Orell A, Hong Y, Peeters E, Albers SV, Charlier D. Microbiologyopen 2 75-93 (2013)
  22. Crystal structure of Mycobacterium tuberculosis LrpA, a leucine-responsive global regulator associated with starvation response. Reddy MC, Gokulan K, Jacobs WR, Ioerger TR, Sacchettini JC. Protein Sci 17 159-170 (2008)
  23. Interactions between the archaeal transcription repressor FL11 and its coregulators lysine and arginine. Yamada M, Ishijima SA, Suzuki M. Proteins 74 520-525 (2009)
  24. Transcriptional activation in the context of repression mediated by archaeal histones. Wilkinson SP, Ouhammouch M, Geiduschek EP. Proc Natl Acad Sci U S A 107 6777-6781 (2010)
  25. Metagenomic analysis of the 1-aminocyclopropane-1-carboxylate deaminase gene (acdS) operon of an uncultured bacterial endophyte colonizing Solanum tuberosum L. Nikolic B, Schwab H, Sessitsch A. Arch Microbiol 193 665-676 (2011)
  26. BarR, an Lrp-type transcription factor in Sulfolobus acidocaldarius, regulates an aminotransferase gene in a β-alanine responsive manner. Liu H, Orell A, Maes D, van Wolferen M, Lindås AC, Bernander R, Albers SV, Charlier D, Peeters E. Mol Microbiol 92 625-639 (2014)
  27. Massively Parallel Fitness Profiling Reveals Multiple Novel Enzymes in Pseudomonas putida Lysine Metabolism. Thompson MG, Blake-Hedges JM, Cruz-Morales P, Barajas JF, Curran SC, Eiben CB, Harris NC, Benites VT, Gin JW, Sharpless WA, Twigg FF, Skyrud W, Krishna RN, Pereira JH, Baidoo EEK, Petzold CJ, Adams PD, Arkin AP, Deutschbauer AM, Keasling JD. mBio 10 (2019)
  28. Insight into the haem d1 biosynthesis pathway in heliobacteria through bioinformatics analysis. Xiong J, Bauer CE, Pancholy A. Microbiology (Reading) 153 3548-3562 (2007)
  29. Ligand-induced structural transitions, mutational analysis, and 'open' quaternary structure of the M. tuberculosis feast/famine regulatory protein (Rv3291c). Shrivastava T, Dey A, Ramachandran R. J Mol Biol 392 1007-1019 (2009)
  30. Regulation of the ald gene encoding alanine dehydrogenase by AldR in Mycobacterium smegmatis. Jeong JA, Baek EY, Kim SW, Choi JS, Oh JI. J Bacteriol 195 3610-3620 (2013)
  31. Silencing of DNase Colicin E8 Gene Expression by a Complex Nucleoprotein Assembly Ensures Timely Colicin Induction. Kamenšek S, Browning DF, Podlesek Z, Busby SJ, Žgur-Bertok D, Butala M. PLoS Genet 11 e1005354 (2015)
  32. New Targets and Cofactors for the Transcription Factor LrpA from Mycobacterium tuberculosis. Song N, Cui Y, Li Z, Chen L, Liu S. DNA Cell Biol 35 167-176 (2016)
  33. The crystal structure of siroheme decarboxylase in complex with iron-uroporphyrin III reveals two essential histidine residues. Haufschildt K, Schmelz S, Kriegler TM, Neumann A, Streif J, Arai H, Heinz DW, Layer G. J Mol Biol 426 3272-3286 (2014)
  34. Crystal Structure of Mycobacterium tuberculosis H37Rv AldR (Rv2779c), a Regulator of the ald Gene: DNA BINDING AND IDENTIFICATION OF SMALL MOLECULE INHIBITORS. Dey A, Shree S, Pandey SK, Tripathi RP, Ramachandran R. J Biol Chem 291 11967-11980 (2016)
  35. Evolution of a global regulator: Lrp in four orders of γ-Proteobacteria. Unoarumhi Y, Blumenthal RM, Matson JS. BMC Evol Biol 16 111 (2016)
  36. Hybrid Ptr2-like activators of archaeal transcription. Pritchett MA, Wilkinson SP, Geiduschek EP, Ouhammouch M. Mol Microbiol 74 582-593 (2009)
  37. Crystal structure of STS042, a stand-alone RAM module protein, from hyperthermophilic archaeon Sulfolobus tokodaii strain 7. Miyazono K, Tsujimura M, Kawarabayasi Y, Tanokura M. Proteins 71 1557-1562 (2008)
  38. HU of Streptococcus pneumoniae Is Essential for the Preservation of DNA Supercoiling. Ferrándiz MJ, Carreño D, Ayora S, de la Campa AG. Front Microbiol 9 493 (2018)
  39. Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family Regulator AldR. Jeong JA, Hyun J, Oh JI. J Bacteriol 197 3142-3153 (2015)
  40. DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers. Soufi A, Sawasdichai A, Shukla A, Noy P, Dafforn T, Smith C, Jayaraman PS, Gaston K. Nucleic Acids Res 38 7513-7525 (2010)
  41. Enhanced production of branched-chain amino acids by Gluconacetobacter europaeus with a specific regional deletion in a leucine responsive regulator. Akasaka N, Ishii Y, Hidese R, Sakoda H, Fujiwara S. J Biosci Bioeng 118 607-615 (2014)
  42. Enhancement of precursor amino acid supplies for improving bacitracin production by activation of branched chain amino acid transporter BrnQ and deletion of its regulator gene lrp in Bacillus licheniformis. Zhu J, Cai D, Xu H, Liu Z, Zhang B, Wu F, Li J, Chen S. Synth Syst Biotechnol 3 236-243 (2018)
  43. The proline rich homeodomain protein PRH/Hhex forms stable oligomers that are highly resistant to denaturation. Shukla A, Burton NM, Jayaraman PS, Gaston K. PLoS One 7 e35984 (2012)
  44. An Lrp-type transcriptional regulator controls expression of the Bacillus subtilis chromate transporter. Aguilar-Barajas E, Jacobo-Arreola S, Verduzco-Rosas LA, Jiménez-Mejía R, Ramírez-Díaz MI, Julián-Sánchez A, Riveros-Rosas H, Cervantes C. Antonie Van Leeuwenhoek 104 941-948 (2013)
  45. Analysis of Haloferax mediterranei Lrp Transcriptional Regulator. Matarredona L, Camacho M, García-Bonete MJ, Esquerra B, Zafrilla B, Esclapez J, Bonete MJ. Genes (Basel) 12 802 (2021)
  46. Regulatory and biosynthetic effects of the bkd gene clusters on the production of daptomycin and its analogs A21978C1-3. Luo S, Chen XA, Mao XM, Li YQ. J Ind Microbiol Biotechnol 45 271-279 (2018)
  47. The Transcriptional Regulator Lrp Contributes to Toxin Expression, Sporulation, and Swimming Motility in Clostridium difficile. Chen KY, Rathod J, Chiu YC, Chen JW, Tsai PJ, Huang IH. Front Cell Infect Microbiol 9 356 (2019)
  48. Escherichia coli Leucine-Responsive Regulatory Protein Bridges DNA In Vivo and Tunably Dissociates in the Presence of Exogenous Leucine. Ziegler CA, Freddolino PL. mBio 14 e0269022 (2023)
  49. Leucine-Responsive Regulatory Protein in Acetic Acid Bacteria Is Stable and Functions at a Wide Range of Intracellular pH Levels. Ishii Y, Shige Y, Akasaka N, Trinugraha AC, Higashikubo H, Fukuda W, Fujiwara S. J Bacteriol 203 e0016221 (2021)
  50. Molecular mechanisms of regulation by a β-alanine-responsive Lrp-type transcription factor from Acidianus hospitalis. Bernauw AJ, Crabbe V, Ryssegem F, Willaert R, Bervoets I, Peeters E. Microbiologyopen 12 e1356 (2023)
  51. Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors. Purtov YA, Ozoline ON. Int J Mol Sci 24 15863 (2023)
  52. Structural and functional characterization of the bacterial biofilm activator RemA. Hoffmann T, Mrusek D, Bedrunka P, Burchert F, Mais CN, Kearns DB, Altegoer F, Bremer E, Bange G. Nat Commun 12 5707 (2021)
  53. The Lrp/AsnC-Type Regulator PA2577 Controls the EamA-like Transporter Gene PA2576 in Pseudomonas aeruginosa. Modrzejewska M, Kawalek A, Bartosik AA. Int J Mol Sci 22 13340 (2021)
  54. The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development. Kostrouchová M, Kostrouch D, Chughtai AA, Kaššák F, Novotný JP, Kostrouchová V, Benda A, Krause MW, Saudek V, Kostrouchová M, Kostrouch Z. PeerJ 5 e3390 (2017)