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Mechanistic insights from the crystal structures of a feast/famine regulatory protein from Mycobacterium tuberculosis H37Rv.

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Shrivastava T, Ramachandran R
OpenAccess logo Nucleic Acids Res 35 7324-35 (2007)
Related entries: 2ivm, 2vbw, 2vbx, 2vby, 2vbz, 2vc0

Cited: 24 times
EuropePMC logo PMID: 17962306

Abstract

Rv3291c gene from Mycobacterium tuberculosis codes for a transcriptional regulator belonging to the (leucine responsive regulatory protein/regulator of asparigine synthase C gene product) Lrp/AsnC-family. We have identified a novel effector-binding site from crystal structures of the apo protein, complexes with a variety of amino acid effectors, X-ray based ligand screening and qualitative fluorescence spectroscopy experiments. The new effector site is in addition to the structural characterization of another distinct site in the protein conserved in the related AsnC-family of regulators. The structures reveal that the ligand-binding loops of two crystallographically independent subunits adopt different conformations to generate two distinct effector-binding sites. A change in the conformation of the binding site loop 100-106 in the B subunit is apparently necessary for octameric association and also allows the loop to interact with a bound ligand in the newly identified effector-binding site. There are four sites of each kind in the octamer and the protein preferentially binds to aromatic amino acids. While amino acids like Phe, Tyr and Trp exhibit binding to only one site, His exhibits binding to both sites. Binding of Phe is accompanied by a conformational change of 3.7 A in the 75-83 loop, which is advantageously positioned to control formation of higher oligomers. Taken together, the present studies suggest an elegant control mechanism for global transcription regulation involving binding of ligands to the two sites, individually or collectively.

Articles - 2vc1 mentioned but not cited (1)

  1. 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)


Reviews citing this publication (4)

  1. Role of the Extremolytes Ectoine and Hydroxyectoine as Stress Protectants and Nutrients: Genetics, Phylogenomics, Biochemistry, and Structural Analysis. Czech L, Hermann L, Stöveken N, Richter AA, Höppner A, Smits SHJ, Heider J, Bremer E. Genes (Basel) 9 E177 (2018)
  2. Regulatory and pathogenesis roles of Mycobacterium Lrp/AsnC family transcriptional factors. Deng W, Wang H, Xie J. J Cell Biochem 112 2655-2662 (2011)
  3. The leucine-responsive regulatory proteins/feast-famine regulatory proteins: an ancient and complex class of transcriptional regulators in bacteria and archaea. Ziegler CA, Freddolino PL. Crit Rev Biochem Mol Biol 56 373-400 (2021)
  4. Alanine dehydrogenases in mycobacteria. Jeong JA, Oh JI. J Microbiol 57 81-92 (2019)

Articles citing this publication (19)

  1. 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)
  2. 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)
  3. Unexpected coregulator range for the global regulator Lrp of Escherichia coli and Proteus mirabilis. Hart BR, Blumenthal RM. J Bacteriol 193 1054-1064 (2011)
  4. Cell density-induced changes in lipid composition and intracellular trafficking. Kavaliauskiene S, Nymark CM, Bergan J, Simm R, Sylvänne T, Simolin H, Ekroos K, Skotland T, Sandvig K. Cell Mol Life Sci 71 1097-1116 (2014)
  5. 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)
  6. Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraea. Liu J, Chen Y, Wang W, Ren M, Wu P, Wang Y, Li C, Zhang L, Wu H, Weaver DT, Zhang B. Metab Eng 39 29-37 (2017)
  7. 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)
  8. Transcriptional regulation of ectoine catabolism in response to multiple metabolic and environmental cues. Schulz A, Hermann L, Freibert SA, Bönig T, Hoffmann T, Riclea R, Dickschat JS, Heider J, Bremer E. Environ Microbiol 19 4599-4619 (2017)
  9. Structures of replication initiation proteins from staphylococcal antibiotic resistance plasmids reveal protein asymmetry and flexibility are necessary for replication. Carr SB, Phillips SE, Thomas CD. Nucleic Acids Res 44 2417-2428 (2016)
  10. 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)
  11. Interactions between the archaeal transcription repressor FL11 and its coregulators lysine and arginine. Yamada M, Ishijima SA, Suzuki M. Proteins 74 520-525 (2009)
  12. 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)
  13. 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)
  14. 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)
  15. 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)
  16. Competitive Repression of the artPIQM Operon for Arginine and Ornithine Transport by Arginine Repressor and Leucine-Responsive Regulatory Protein in Escherichia coli. Torres Montaguth OE, Bervoets I, Peeters E, Charlier D. Front Microbiol 10 1563 (2019)
  17. 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)
  18. Does long-term use of silver nanoparticles have persistent inhibitory effect on H. pylori based on Mongolian gerbil's model? Kuo CH, Lu CY, Yang YC, Chin C, Weng BC, Liu CJ, Chen YH, Chang LL, Kuo FC, Wu DC, Su HL. Biomed Res Int 2014 461034 (2014)
  19. Withdrawn Infect Disord Drug Targets (2012)


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