The Aspartate-Less Receiver (ALR) Domains: Distribution, Structure and Function

English version České info

Two-Component Signaling (TCS) systems are a primary means by which bacteria sense their constantly changing external environment. For pathogens, these relays are key to their host survival. A typical TCS pair consists of a sensor protein, which upon an environmental stimulation will initiate a cellular response by transferring a phosphate group onto a crucial aspartate amino acid within a secondary receiver (REC) protein. However, more recently it has come to light that some REC proteins are missing key amino acids involved in this signaling relay process, including the aspartate residue required for the signaling relay, hinting that a subset of REC proteins might function in different ways. Here we use custom programing to extract all deposited Aspartate-Less Receivers (ALRs) for further examination. Surprisingly, we found that on average there are two ALRs present in every microbial species, making them a significant portion of the bacterial signaling family. Combining computational data with structural, biochemical and genetic examination of a founding member of the ALR family, Repressor of Iron Transport Regulator (RitR) from the human pathogen Streptococcus pneumoniae, we demonstrate that ALRs might have evolved to accommodate more diverse environmental signals, while largely retaining their time-tested ancestral post-input signaling mechanisms.

Vyšlo v časopise: The Aspartate-Less Receiver (ALR) Domains: Distribution, Structure and Function. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004795
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004795

Souhrn

Zdroje

1. Ulrich LE, Koonin EV, Zhulin IB (2005) One-component systems dominate signal transduction in prokaryotes. Trends Microbiol 13: 52–56. 15680762

2. Hoch JA, Silhavy TJ, editors (1995) Two-component signal transduction. Washington, D.C.: American Society for Microbiology.

3. Bourret RB, Silversmith RE (2010) Two-component signal transduction. Curr Opin Microbiol 13: 113–115. doi: 10.1016/j.mib.2010.02.003 20219418

4. Gao R, Stock AM (2009) Biological insights from structures of two-component proteins. Annu Rev Microbiol 63: 133–154. doi: 10.1146/annurev.micro.091208.073214 19575571

5. Volkman BF, Lipson D, Wemmer DE, Kern D (2001) Two-state allosteric behavior in a single-domain signaling protein. Science 291: 2429–2433. 11264542

6. Feher VA, Cavanagh J (1999) Millisecond-timescale motions contribute to the function of the bacterial response regulator protein Spo0F. Nature 400: 289–293. 10421374

7. Dyer CM, Dahlquist FW (2006) Switched or not?: the structure of unphosphorylated CheY bound to the N terminus of FliM. J Bacteriol 188: 7354–7363. 17050923

8. Gardino AK, Villali J, Kivenson A, Lei M, Liu CF, et al. (2009) Transient non-native hydrogen bonds promote activation of a signaling protein. Cell 139: 1109–1118. doi: 10.1016/j.cell.2009.11.022 20005804

9. Bourret RB (2010) Receiver domain structure and function in response regulator proteins. Curr Opin Microbiol 13: 142–149. doi: 10.1016/j.mib.2010.01.015 20211578

10. Lee SY, Cho HS, Pelton JG, Yan D, Berry EA, et al. (2001) Crystal structure of activated CheY. Comparison with other activated receiver domains. J Biol Chem 276: 16425–16431. 11279165

11. Schuster M, Silversmith RE, Bourret RB (2001) Conformational coupling in the chemotaxis response regulator CheY. Proc Natl Acad Sci U S A 98: 6003–6008. 11353835

12. Zhu X, Volz K, Matsumura P (1997) The CheZ-binding surface of CheY overlaps the CheA- and FliM-binding surfaces. J Biol Chem 272: 23758–23764. 9295320

13. Toro-Roman A, Mack TR, Stock AM (2005) Structural analysis and solution studies of the activated regulatory domain of the response regulator ArcA: a symmetric dimer mediated by the alpha4-beta5-alpha5 face. J Mol Biol 349: 11–26. 15876365

14. Toro-Roman A, Wu T, Stock AM (2005) A common dimerization interface in bacterial response regulators KdpE and TorR. Protein Sci 14: 3077–3088. 16322582

15. Leonard PG, Golemi-Kotra D, Stock AM (2013) Phosphorylation-dependent conformational changes and domain rearrangements in Staphylococcus aureus VraR activation. Proc Natl Acad Sci U S A 110: 8525–8530. doi: 10.1073/pnas.1302819110 23650349

16. Trajtenberg F, Albanesi D, Ruetalo N, Botti H, Mechaly AE, et al. (2014) Allosteric activation of bacterial response regulators: the role of the cognate histidine kinase beyond phosphorylation. MBio 5: 2105–2114.

17. O'Hara BP, Norman RA, Wan PT, Roe SM, Barrett TE, et al. (1999) Crystal structure and induction mechanism of AmiC-AmiR: a ligand-regulated transcription antitermination complex. EMBO J 18: 5175–5186. 10508151

18. Galperin MY (2006) Structural classification of bacterial response regulators: diversity of output domains and domain combinations. J Bacteriol 188: 4169–4182. 16740923

19. Gao R, Stock AM (2010) Molecular strategies for phosphorylation-mediated regulation of response regulator activity. Curr Opin Microbiol 13: 160–167. doi: 10.1016/j.mib.2009.12.009 20080056

20. Wang L, Tian X, Wang J, Yang H, Fan K, et al. (2009) Autoregulation of antibiotic biosynthesis by binding of the end product to an atypical response regulator. Proc Natl Acad Sci U S A 106: 8617–8622. doi: 10.1073/pnas.0900592106 19423672

21. Burnside K, Rajagopal L (2012) Regulation of prokaryotic gene expression by eukaryotic-like enzymes. Curr Opin Microbiol 15: 125–131. doi: 10.1016/j.mib.2011.12.006 22221896

22. Lin WJ, Walthers D, Connelly JE, Burnside K, Jewell KA, et al. (2009) Threonine phosphorylation prevents promoter DNA binding of the Group B Streptococcus response regulator CovR. Mol Microbiol 71: 1477–1495. doi: 10.1111/j.1365-2958.2009.06616.x 19170889

23. Ulijasz AT, Andes DR, Glasner JD, Weisblum B (2004) Regulation of iron transport in Streptococcus pneumoniae by RitR, an orphan response regulator. J Bacteriol 186: 8123–8136. 15547286

24. Ulijasz AT, Falk SP, Weisblum B (2009) Phosphorylation of the RitR DNA-binding domain by a Ser-Thr phosphokinase: implications for global gene regulation in the streptococci. Mol Microbiol 71: 382–390. doi: 10.1111/j.1365-2958.2008.06532.x 19040630

25. Schar J, Sickmann A, Beier D (2005) Phosphorylation-independent activity of atypical response regulators of Helicobacter pylori. J Bacteriol 187: 3100–3109. 15838037

26. Koo IC, Walthers D, Hefty PS, Kenney LJ, Stephens RS (2006) ChxR is a transcriptional activator in Chlamydia. Proc Natl Acad Sci U S A 103: 750–755. 16407127

27. Hickey JM, Weldon L, Hefty PS (2011) The atypical OmpR/PhoB response regulator ChxR from Chlamydia trachomatis forms homodimers in vivo and binds a direct repeat of nucleotide sequences. J Bacteriol 193: 389–398. doi: 10.1128/JB.00833-10 21057008

28. Fraser JS, Merlie JP Jr., Echols N, Weisfield SR, Mignot T, et al. (2007) An atypical receiver domain controls the dynamic polar localization of the Myxococcus xanthus social motility protein FrzS. Mol Microbiol 65: 319–332. 17573816

29. Williams SB, Vakonakis I, Golden SS, LiWang AC (2002) Structure and function from the circadian clock protein KaiA of Synechococcus elongatus: a potential clock input mechanism. Proc Natl Acad Sci U S A 99: 15357–15362. 12438647

30. Kolmos E, Schoof H, Plumer M, Davis SJ (2008) Structural insights into the function of the core-circadian factor TIMING OF CAB2 EXPRESSION 1 (TOC1). J Circadian Rhythms 6: 3. doi: 10.1186/1740-3391-6-3 18298828

31. Klose KE, Weiss DS, Kustu S (1993) Glutamate at the site of phosphorylation of nitrogen-regulatory protein NTRC mimics aspartyl-phosphate and activates the protein. J Mol Biol 232: 67–78. 8331671

32. Gao R, Mukhopadhyay A, Fang F, Lynn DG (2006) Constitutive activation of two-component response regulators: characterization of VirG activation in Agrobacterium tumefaciens. J Bacteriol 188: 5204–5211. 16816192

33. Arribas-Bosacoma R, Kim S-K, Ferrer-Orta C, Blanco AG, Pereira PJB, et al. (2007) The X-ray Crystal Structures of Two Constitutively Active Mutants of the Escherichia coli PhoB Receiver Domain Give Insights into Activation. J Mol Biol 366: 626–641. 17182055

34. Bourret RB, Hess JF, Simon MI (1990) Conserved aspartate residues and phosphorylation in signal transduction by the chemotaxis protein CheY. Proc Natl Acad Sci U S A 87: 41–45. 2404281

35. Zundel CJ, Capener DC, McCleary WR (1998) Analysis of the conserved acidic residues in the regulatory domain of PhoB. FEBS Lett 441: 242–246. 9883892

36. Green BD, Olmedo G, Youngman P (1991) A genetic analysis of Spo0A structure and function. Res Microbiol 142: 825–830. 1664535

37. Hickey JM, Lovell S, Battaile KP, Hu L, Middaugh CR, et al. (2011) The atypical response regulator protein ChxR has structural characteristics and dimer interface interactions that are unique within the OmpR/PhoB subfamily. J Biol Chem 286: 32606–32616. doi: 10.1074/jbc.M111.220574 21775428

38. Hong E, Lee HM, Ko H, Kim DU, Jeon BY, et al. (2007) Structure of an atypical orphan response regulator protein supports a new phosphorylation-independent regulatory mechanism. J Biol Chem 282: 20667–20675. 17491010

39. Attwood PV, Besant PG, Piggott MJ (2011) Focus on phosphoaspartate and phosphoglutamate. Amino Acids 40: 1035–1051. doi: 10.1007/s00726-010-0738-5 20859643

40. Nishiyama SI, Umemura T, Nara T, Homma M, Kawagishi I (1999) Conversion of a bacterial warm sensor to a cold sensor by methylation of a single residue in the presence of an attractant. Mol Microbiol 32: 357–365. 10231491

41. Wolanin PM, Webre DJ, Stock JB (2003) Mechanism of phosphatase activity in the chemotaxis response regulator CheY. Biochemistry 42: 14075–14082. 14636076

42. Wright DP, Ulijasz AT Regulation of transcription by eukaryotic-like serine-threonine kinases and phosphatases in Gram-positive bacterial pathogens. Virulence 5: 863–865. doi: 10.4161/21505594.2014.983404 25603430

43. Grangeasse C, Nessler S, Mijakovic I (2012) Bacterial tyrosine kinases: evolution, biological function and structural insights. Philos Trans R Soc Lond B Biol Sci 367: 2640–2655. doi: 10.1098/rstb.2011.0424 22889913

44. Fuhrmann J, Schmidt A, Spiess S, Lehner A, Turgay K, et al. (2009) McsB is a protein arginine kinase that phosphorylates and inhibits the heat-shock regulator CtsR. Science 324: 1323–1327. doi: 10.1126/science.1170088 19498169

45. Elsholz AK, Turgay K, Michalik S, Hessling B, Gronau K, et al. (2012) Global impact of protein arginine phosphorylation on the physiology of Bacillus subtilis. Proc Natl Acad Sci U S A 109: 7451–7456. doi: 10.1073/pnas.1117483109 22517742

46. Antelmann H, Helmann JD (2011) Thiol-based redox switches and gene regulation. Antioxid Redox Signal 14: 1049–1063. doi: 10.1089/ars.2010.3400 20626317

47. Heras B, Shouldice SR, Totsika M, Scanlon MJ, Schembri MA, et al. (2009) DSB proteins and bacterial pathogenicity. Nat Rev Microbiol 7: 215–225. doi: 10.1038/nrmicro2087 19198617

48. Pereira SF, Goss L, Dworkin J (2011) Eukaryote-like serine/threonine kinases and phosphatases in bacteria. Microbiol Mol Biol Rev 75: 192–212. doi: 10.1128/MMBR.00042-10 21372323

49. Driscoll T, Gillespie JJ, Nordberg EK, Azad AF, Sobral BW (2013) Bacterial DNA sifted from the Trichoplax adhaerens (Animalia: Placozoa) genome project reveals a putative rickettsial endosymbiont. Genome Biol Evol 5: 621–645. doi: 10.1093/gbe/evt036 23475938

50. Kenney LJ (2002) Structure/function relationships in OmpR and other winged-helix transcription factors. Curr Opin Microbiol 5: 135–141. 11934608

51. Volkman BF, Nohaile MJ, Amy NK, Kustu S, Wemmer DE (1995) Three-dimensional solution structure of the N-terminal receiver domain of NTRC. Biochemistry 34: 1413–1424. 7827089

52. Menon S, Wang S (2011) Structure of the response regulator PhoP from Mycobacterium tuberculosis reveals a dimer through the receiver domain. Biochemistry 50: 5948–5957. doi: 10.1021/bi2005575 21634789

53. Buckler DR, Zhou Y, Stock AM (2002) Evidence of intradomain and interdomain flexibility in an OmpR/PhoB homolog from Thermotoga maritima. Structure 10: 153–164. 11839301

54. Villali J, Pontiggia F, Clarkson MW, Hagan MF, Kern D (2014) Evidence against the "Y-T coupling" mechanism of activation in the response regulator NtrC. J Mol Biol 426: 1554–1567. doi: 10.1016/j.jmb.2013.12.027 24406745

55. Wood TL, Bridwell-Rabb J, Kim YI, Gao T, Chang YG, et al. (2010) The KaiA protein of the cyanobacterial circadian oscillator is modulated by a redox-active cofactor. Proc Natl Acad Sci U S A 107: 5804–5809. doi: 10.1073/pnas.0910141107 20231482

56. Ong CL, Potter AJ, Trappetti C, Walker MJ, Jennings MP, et al. (2013) Interplay between manganese and iron in pneumococcal pathogenesis: role of the orphan response regulator RitR. Infect Immun 81: 421–429. doi: 10.1128/IAI.00805-12 23184523

57. Birck C, Mourey L, Gouet P, Fabry B, Schumacher J, et al. (1999) Conformational changes induced by phosphorylation of the FixJ receiver domain. Structure 7: 1505–1515. 10647181

58. Park S, Meyer M, Jones AD, Yennawar HP, Yennawar NH, et al. (2002) Two-component signaling in the AAA + ATPase DctD: binding Mg2+ and BeF3- selects between alternate dimeric states of the receiver domain. FASEB J 16: 1964–1966. 12368235

59. Finn RD, Mistry J, Tate J, Coggill P, Heger A, et al. (2010) The Pfam protein families database. Nucleic Acids Res 38: D211–222. doi: 10.1093/nar/gkp985 19920124

60. Cock PJ, Antao T, Chang JT, Chapman BA, Cox CJ, et al. (2009) Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25: 1422–1423. doi: 10.1093/bioinformatics/btp163 19304878

61. EMBL (2012) Reorganizing the protein space at the Universal Protein Resource (UniProt). Nucleic Acids Res 40: D71–75. doi: 10.1093/nar/gkr981 22102590

62. Sung CK, Li H, Claverys JP, Morrison DA (2001) An rpsL cassette, janus, for gene replacement through negative selection in Streptococcus pneumoniae. Appl Environ Microbiol 67: 5190–5196. 11679344

63. Weng L, Biswas I, Morrison DA (2009) A self-deleting Cre-lox-ermAM cassette, Cheshire, for marker-less gene deletion in Streptococcus pneumoniae. J Microbiol Methods 79: 353–357. doi: 10.1016/j.mimet.2009.10.007 19850089

64. Halfmann A, Hakenbeck R, Bruckner R (2007) A new integrative reporter plasmid for Streptococcus pneumoniae. FEMS Microbiol Lett 268: 217–224. 17328748

65. Lefevre JC, Claverys JP, Sicard AM (1979) Donor deoxyribonucleic acid length and marker effect in pneumococcal transformation. J Bacteriol 138: 80–86. 35523

66. Ulijasz AT, Grenader A, Weisblum B (1996) A vancomycin-inducible lacZ reporter system in Bacillus subtilis: induction by antibiotics that inhibit cell wall synthesis and by lysozyme. J Bacteriol 178: 6305–6309. 8892834

67. Otwinowski Z, Minor W, editors (1997) Processing of X-ray Diffraction Data Collected in Oscillation Mode. New York: Academic Press. 307–326 p.

68. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, et al. (2007) Phaser crystallographic software. J Appl Crystallogr 40: 658–674. 19461840

69. Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, et al. (2011) Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr 67: 235–242. doi: 10.1107/S0907444910045749 21460441

70. Birck C, Chen Y, Hulett FM, Samama JP (2003) The crystal structure of the phosphorylation domain in PhoP reveals a functional tandem association mediated by an asymmetric interface. J Bacteriol 185: 254–261. 12486062

71. Terwilliger TC, Grosse-Kunstleve RW, Afonine PV, Moriarty NW, Zwart PH, et al. (2008) Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr D Biol Crystallogr 64: 61–69. 18094468

72. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213–221. doi: 10.1107/S0907444909052925 20124702

73. Afonine PV, Mustyakimov M, Grosse-Kunstleve RW, Moriarty NW, Langan P, et al. (2010) Joint X-ray and neutron refinement with phenix.refine. Acta Crystallogr D Biol Crystallogr 66: 1153–1163. doi: 10.1107/S0907444910026582 21041930

74. Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60: 2126–2132. 15572765

75. Word JM, Lovell SC, Richardson JS, Richardson DC (1999) Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation. J Mol Biol 285: 1735–1747. 9917408

76. Painter J, Merritt EA (2005) A molecular viewer for the analysis of TLS rigid-body motion in macromolecules. Acta Crystallogr D Biol Crystallogr 61: 465–471. 15809496

77. Chen VB, Arendall WB 3rd, Headd JJ, Keedy DA, Immormino RM, et al. (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66: 12–21. doi: 10.1107/S0907444909042073 20057044

78. Cavanagh J, Palmer AG III, Fairbrother W, Skelton NJ (2007) Protein NMR Spectroscopy: Principles and Practice (2nd ed.). Boston: Academic Press.

79. Bartels C, Guntert P, Billeter M, Wuthrich K (1997) GARANT—A general algorithm for resonance assignment of multidimensional nuclear magnetic resonance spectra. J Comput Chem 18: 139–149.

80. Bartels C, Xia TH, Billeter M, Guntert P, Wuthrich K (1995) The program Xeasy for computer-supported NMR spectral-analysis of biological macromolecules. J Biomol NMR 6: 1–10. doi: 10.1007/BF00417486 22911575

81. Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9: 671–675. 22930834

82. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, et al. (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23: 2947–2948. 17846036

83. Han MV, Zmasek CM (2009) phyloXML: XML for evolutionary biology and comparative genomics. BMC Bioinformatics 10: 356. doi: 10.1186/1471-2105-10-356 19860910

84. Schwede T, Kopp J, Guex N, Peitsch MC (2003) SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res 31: 3381–3385. 12824332