2pbx Citations

Crystal structure of the Vibrio cholerae quorum-sensing regulatory protein HapR.

J. Bacteriol. 189 5683-91 (2007)
Cited: 40 times
EuropePMC logo PMID: 17526705


Quorum sensing in Vibrio cholerae involves signaling between two-component sensor protein kinases and the response regulator LuxO to control the expression of the master regulator HapR. HapR, in turn, plays a central role in regulating a number of important processes, such as virulence gene expression and biofilm formation. We have determined the crystal structure of HapR to 2.2-A resolution. Its structure reveals a dimeric, two-domain molecule with an all-helical structure that is strongly conserved with members of the TetR family of transcriptional regulators. The N-terminal DNA-binding domain contains a helix-turn-helix DNA-binding motif and alteration of certain residues in this domain completely abolishes the ability of HapR to bind to DNA, alleviating repression of both virulence gene expression and biofilm formation. The C-terminal dimerization domain contains a unique solvent accessible tunnel connected to an amphipathic cavity, which by analogy with other TetR regulators, may serve as a binding pocket for an as-yet-unidentified ligand.

Reviews - 2pbx mentioned but not cited (1)

  1. Quorum Sensing Gene Regulation by LuxR/HapR Master Regulators in Vibrios. Ball AS, Chaparian RR, van Kessel JC. J. Bacteriol. 199 (2017)

Articles - 2pbx mentioned but not cited (8)

  1. Crystal structure of the Vibrio cholerae quorum-sensing regulatory protein HapR. De Silva RS, Kovacikova G, Lin W, Taylor RK, Skorupski K, Kull FJ. J. Bacteriol. 189 5683-5691 (2007)
  2. Crystal structure of SmcR, a quorum-sensing master regulator of Vibrio vulnificus, provides insight into its regulation of transcription. Kim Y, Kim BS, Park YJ, Choi WC, Hwang J, Kang BS, Oh TK, Choi SH, Kim MH. J. Biol. Chem. 285 14020-14030 (2010)
  3. Structural plasticity and distinct drug-binding modes of LfrR, a mycobacterial efflux pump regulator. Bellinzoni M, Buroni S, Schaeffer F, Riccardi G, De Rossi E, Alzari PM. J. Bacteriol. 191 7531-7537 (2009)
  4. Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. Carter JD, Gonzales EG, Huang X, Smith AN, de Vera IM, D'Amore PW, Rocca JR, Goodenow MM, Dunn BM, Fanucci GE. FEBS Lett. 588 3123-3128 (2014)
  5. Evidence on how a conserved glycine in the hinge region of HapR regulates its DNA binding ability: lessons from a natural variant. Dongre M, Singh NS, Dureja C, Peddada N, Solanki AK, Ashish, Raychaudhuri S. J. Biol. Chem. 286 15043-15049 (2011)
  6. Unraveling the specific regulation of the central pathway for anaerobic degradation of 3-methylbenzoate. Juárez JF, Liu H, Zamarro MT, McMahon S, Liu H, Naismith JH, Eberlein C, Boll M, Carmona M, Díaz E. J. Biol. Chem. 290 12165-12183 (2015)
  7. Substitution of glutamate residue by lysine in the dimerization domain affects DNA binding ability of HapR by inducing structural deformity in the DNA binding domain. Singh R, Rathore YS, Singh NS, Peddada N, Ashish, Raychaudhuri S. PLoS ONE 8 e76033 (2013)
  8. Crystal structure of an inactive variant of the quorum-sensing master regulator HapR from the protease-deficient non-O1, non-O139 Vibrio cholerae strain V2. Cruite J, Succo P, Raychaudhuri S, Kull FJ. Acta Crystallogr F Struct Biol Commun 74 331-336 (2018)

Reviews citing this publication (8)

  1. Relationships between the Regulatory Systems of Quorum Sensing and Multidrug Resistance. Xu GM. Front Microbiol 7 958 (2016)
  2. Living in the matrix: assembly and control of Vibrio cholerae biofilms. Teschler JK, Zamorano-Sánchez D, Utada AS, Warner CJ, Wong GC, Linington RG, Yildiz FH. Nat. Rev. Microbiol. 13 255-268 (2015)
  3. Meddling Vibrio cholerae Murmurs: A Neoteric Advancement in Cholera Research. Hema M, Balasubramanian S, Princy SA. Indian J. Microbiol. 55 121-130 (2015)
  4. The TetR family of regulators. Cuthbertson L, Nodwell JR. Microbiol. Mol. Biol. Rev. 77 440-475 (2013)
  5. Combating biofilms. Yang L, Liu Y, Wu H, Song Z, Høiby N, Molin S, Givskov M. FEMS Immunol. Med. Microbiol. 65 146-157 (2012)
  6. Vibrio cholerae infection, novel drug targets and phage therapy. Fazil MH, Singh DV. Future Microbiol 6 1199-1208 (2011)
  7. Design principles of the bacterial quorum sensing gene networks. Goryachev AB. Wiley Interdiscip Rev Syst Biol Med 1 45-60 (2009)
  8. Structures of AcrR and CmeR: insight into the mechanisms of transcriptional repression and multi-drug recognition in the TetR family of regulators. Routh MD, Su CC, Zhang Q, Yu EW. Biochim. Biophys. Acta 1794 844-851 (2009)

Articles citing this publication (23)

  1. Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT. Waters CM, Lu W, Rabinowitz JD, Bassler BL. J. Bacteriol. 190 2527-2536 (2008)
  2. The Vibrio harveyi master quorum-sensing regulator, LuxR, a TetR-type protein is both an activator and a repressor: DNA recognition and binding specificity at target promoters. Pompeani AJ, Irgon JJ, Berger MF, Bulyk ML, Wingreen NS, Bassler BL. Mol. Microbiol. 70 76-88 (2008)
  3. A negative feedback loop involving small RNAs accelerates Vibrio cholerae's transition out of quorum-sensing mode. Svenningsen SL, Waters CM, Bassler BL. Genes Dev. 22 226-238 (2008)
  4. Quorum sensing and a global regulator TsrA control expression of type VI secretion and virulence in Vibrio cholerae. Zheng J, Shin OS, Cameron DE, Mekalanos JJ. Proc. Natl. Acad. Sci. U.S.A. 107 21128-21133 (2010)
  5. A small-RNA-mediated negative feedback loop controls quorum-sensing dynamics in Vibrio harveyi. Tu KC, Waters CM, Svenningsen SL, Bassler BL. Mol. Microbiol. 70 896-907 (2008)
  6. Regulatory targets of quorum sensing in Vibrio cholerae: evidence for two distinct HapR-binding motifs. Tsou AM, Cai T, Liu Z, Zhu J, Kulkarni RV. Nucleic Acids Res. 37 2747-2756 (2009)
  7. A consensus sequence for binding of SmcR, a Vibrio vulnificus LuxR homologue, and genome-wide identification of the SmcR regulon. Lee DH, Jeong HS, Jeong HG, Kim KM, Kim H, Choi SH. J. Biol. Chem. 283 23610-23618 (2008)
  8. Structure-activity relationship of cinnamaldehyde analogs as inhibitors of AI-2 based quorum sensing and their effect on virulence of Vibrio spp. Brackman G, Celen S, Hillaert U, Van Calenbergh S, Cos P, Maes L, Nelis HJ, Coenye T. PLoS ONE 6 e16084 (2011)
  9. Analysis of activator and repressor functions reveals the requirements for transcriptional control by LuxR, the master regulator of quorum sensing in Vibrio harveyi. van Kessel JC, Ulrich LE, Zhulin IB, Bassler BL. MBio 4 (2013)
  10. The VarS/VarA two-component system modulates the activity of the Vibrio cholerae quorum-sensing transcriptional regulator HapR. Tsou AM, Liu Z, Cai T, Zhu J. Microbiology (Reading, Engl.) 157 1620-1628 (2011)
  11. A quorum sensing-disrupting brominated thiophenone with a promising therapeutic potential to treat luminescent vibriosis. Defoirdt T, Benneche T, Brackman G, Coenye T, Sorgeloos P, Scheie AA. PLoS ONE 7 e41788 (2012)
  12. Interplay among cyclic diguanylate, HapR, and the general stress response regulator (RpoS) in the regulation of Vibrio cholerae hemagglutinin/protease. Wang H, Wu JH, Ayala JC, Benitez JA, Silva AJ. J. Bacteriol. 193 6529-6538 (2011)
  13. TetR-type transcriptional regulator VtpR functions as a global regulator in Vibrio tubiashii. Hasegawa H, Häse CC. Appl. Environ. Microbiol. 75 7602-7609 (2009)
  14. Diversity of Clinical and Environmental Isolates of Vibrio cholerae in Natural Transformation and Contact-Dependent Bacterial Killing Indicative of Type VI Secretion System Activity. Bernardy EE, Turnsek MA, Wilson SK, Tarr CL, Hammer BK. Appl. Environ. Microbiol. 82 2833-2842 (2016)
  15. The LuxR-type regulator VpsT negatively controls the transcription of rpoS, encoding the general stress response regulator, in Vibrio cholerae biofilms. Wang H, Ayala JC, Benitez JA, Silva AJ. J. Bacteriol. 196 1020-1030 (2014)
  16. Integration host factor and LuxR synergistically bind DNA to coactivate quorum-sensing genes in Vibrio harveyi. Chaparian RR, Olney SG, Hustmyer CM, Rowe-Magnus DA, van Kessel JC. Mol. Microbiol. 101 823-840 (2016)
  17. Nanotransportation system for cholera toxin in Vibrio cholerae 01. Aoki H, Wu H, Nakano T, Ooi Y, Daikoku E, Kohno T, Matsushita T, Sano K. Med Mol Morphol 42 40-46 (2009)
  18. The master quorum-sensing regulators LuxR/HapR directly interact with the alpha subunit of RNA polymerase to drive transcription activation in Vibrio harveyi and Vibrio cholerae. Ball AS, van Kessel JC. Mol Microbiol 111 1317-1334 (2019)
  19. QStatin, a Selective Inhibitor of Quorum Sensing in Vibrio Species. Kim BS, Jang SY, Bang YJ, Hwang J, Koo Y, Jang KK, Lim D, Kim MH, Choi SH. MBio 9 (2018)
  20. The length of glycine-rich linker in DNA-binding domain is critical for optimal functioning of quorum-sensing master regulatory protein HapR. Singh NS, Kachhap S, Singh R, Mishra RC, Singh B, Raychaudhuri S. Mol. Genet. Genomics 289 1171-1182 (2014)
  21. Arginine 37 of Glycine Linker Dictates Regulatory Function of HapR. Ekka M, Mondal A, Singh R, Sen H, Datta S, Raychaudhuri S. Front Microbiol 11 1949 (2020)
  22. Crystallization and preliminary X-ray diffraction analysis of the TetR-family transcriptional repressor YhgD from Bacillus halodurans. Yeo HK, Park YW, Kang J, Lee JY. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 69 532-534 (2013)
  23. Structure of the inositol-1-phosphate cytidylyltransferase from Thermotoga maritima. Kurnasov OV, Luk HJ, Roberts MF, Stec B. Acta Crystallogr. D Biol. Crystallogr. 69 1808-1817 (2013)