Journal of Structural and Functional Genomics

, Volume 13, Issue 4, pp 233–239 | Cite as

The crystal structures of the α-subunit of the α2β2 tetrameric Glycyl-tRNA synthetase

  • Kemin Tan
  • Min Zhou
  • Rongguang Zhang
  • Wayne F. Anderson
  • Andrzej Joachimiak
Article

Abstract

Aminoacyl-tRNA synthetases (AARSs) are ligases (EC.6.1.1.-) that catalyze the acylation of amino acids to their cognate tRNAs in the process of translating genetic information from mRNA to protein. Their amino acid and tRNA specificity are crucial for correctly translating the genetic code. Glycine is the smallest amino acid and the glycyl-tRNA synthetase (GlyRS) belongs to Class II AARSs. The enzyme is unusual because it can assume different quaternary structures. In eukaryotes, archaebacteria and some bacteria, it forms an α2 homodimer. In some bacteria, GlyRS is an α2β2 heterotetramer and shows a distant similarity to α2 GlyRSs. The human pathogen eubacterium Campylobacter jejuni GlyRS (CjGlyRS) is an α2β2 heterotetramer and is similar to Escherichia coli GlyRS; both are members of Class IIc AARSs. The two-step aminoacylation reaction of tetrameric GlyRSs requires the involvement of both α- and β-subunits. At present, the structure of the GlyRS α2β2 class and the details of the enzymatic mechanism of this enzyme remain unknown. Here we report the crystal structures of the catalytic α-subunit of CjGlyRS and its complexes with ATP, and ATP and glycine. These structures provide detailed information on substrate binding and show evidence for a proposed mechanism for amino acid activation and the formation of the glycyl-adenylate intermediate for Class II AARSs.

Keywords

Gly-tRNA synthetase Catalytic subunit ATP binding Glycine binding 

References

  1. 1.
    Carter CW Jr (1993) Annu Rev Biochem 62:715–748PubMedCrossRefGoogle Scholar
  2. 2.
    Szymanski M, Deniziak MA, Barciszewski J (2001) Nucleic Acids Res 29:288–290PubMedCrossRefGoogle Scholar
  3. 3.
    Hausmann CD, Ibba M (2008) FEMS Microbiol Rev 32:705–721PubMedCrossRefGoogle Scholar
  4. 4.
    Park SG, Schimmel P, Kim S (2008) Proc Natl Acad Sci USA 105:11043–11049PubMedCrossRefGoogle Scholar
  5. 5.
    Nagel GM, Doolittle RF (1991) Proc Natl Acad Sci USA 88:8121–8125PubMedCrossRefGoogle Scholar
  6. 6.
    Eriani G, Delarue M, Poch O, Gangloff J, Moras D (1990) Nature 347:203–206PubMedCrossRefGoogle Scholar
  7. 7.
    Moras D (1992) Trends Biochem Sci 17:159–164PubMedCrossRefGoogle Scholar
  8. 8.
    Ostrem DL, Berg P (1974) Biochemistry 13:1338–1348PubMedCrossRefGoogle Scholar
  9. 9.
    Surguchov AP, Surguchova IG (1975) Eur J Biochem 54:175–184PubMedCrossRefGoogle Scholar
  10. 10.
    Kern D, Giege R, Ebel JP (1981) Biochemistry 20:122–131PubMedCrossRefGoogle Scholar
  11. 11.
    Nada S, Chang PK, Dignam JD (1993) J Biol Chem 268:7660–7667PubMedGoogle Scholar
  12. 12.
    Ge Q, Trieu EP, Targoff IN (1994) J Biol Chem 269:28790–28797PubMedGoogle Scholar
  13. 13.
    Tang SN, Huang JF (2005) FEBS Lett 579:1441–1445PubMedCrossRefGoogle Scholar
  14. 14.
    Parkhill J, Wren BW, Mungall K, Ketley JM, Churcher C, Basham D, Chillingworth T, Davies RM, Feltwell T, Holroyd S, Jagels K, Karlyshev AV, Moule S, Pallen MJ, Penn CW, Quail MA, Rajandream MA, Rutherford KM, van Vliet AH, Whitehead S, Barrell BG (2000) Nature 403:665–668PubMedCrossRefGoogle Scholar
  15. 15.
    Chan VL, Bingham HL (1992) J Bacteriol 174:695–701PubMedGoogle Scholar
  16. 16.
    Hong Y, Wong T, Bourke B, Chan VL (1995) Microbiology 141(Pt 10):2561–2567PubMedCrossRefGoogle Scholar
  17. 17.
    Toth MJ, Schimmel P (1990) J Biol Chem 265:1000–1004PubMedGoogle Scholar
  18. 18.
    Toth MJ, Schimmel P (1990) J Biol Chem 265:1005–1009PubMedGoogle Scholar
  19. 19.
    Logan DT, Mazauric MH, Kern D, Moras D (1995) EMBO J 14:4156–4167PubMedGoogle Scholar
  20. 20.
    Arnez JG, Dock-Bregeon AC, Moras D (1999) J Mol Biol 286:1449–1459PubMedCrossRefGoogle Scholar
  21. 21.
    Cader MZ, Ren J, James PA, Bird LE, Talbot K, Stammers DK (2007) FEBS Lett 581:2959–2964PubMedCrossRefGoogle Scholar
  22. 22.
    Xie W, Nangle LA, Zhang W, Schimmel P, Yang XL (2007) Proc Natl Acad Sci USA 104:9976–9981PubMedCrossRefGoogle Scholar
  23. 23.
    Guo RT, Chong YE, Guo M, Yang XL (2009) J Biol Chem 284:28968–28976PubMedCrossRefGoogle Scholar
  24. 24.
    Kim Y, Dementieva I, Zhou M, Wu R, Lezondra L, Quartey P, Joachimiak G, Korolev O, Li H, Joachimiak A (2004) J Struct Funct Genomics 5:111–118PubMedCrossRefGoogle Scholar
  25. 25.
    Tan K, Li H, Zhang R, Gu M, Clancy ST, Joachimiak A (2008) J Struct Biol 162:94–107PubMedCrossRefGoogle Scholar
  26. 26.
    Minor W, Cymborowski M, Otwinowski Z, Chruszcz M (2006) Acta Crystallogr A 62:859–866Google Scholar
  27. 27.
    Vagin AA, Teplyakov A (1997) J Appl Crystallogr 30:1022–1025CrossRefGoogle Scholar
  28. 28.
    Emsley P, Cowtan K (2004) Acta Crystallogr A 60:2126–2132Google Scholar
  29. 29.
    Murshudov GN, Vagin AA, Dodson EJ (1997) Acta Crystallogr A 53:240–255Google Scholar
  30. 30.
    Krissinel E, Henrick K (2007) J Mol Biol 372:774–797PubMedCrossRefGoogle Scholar
  31. 31.
    Cusack S (1993) Biochimie 75:1077–1081PubMedCrossRefGoogle Scholar
  32. 32.
    Shiba K, Schimmel P, Motegi H, Noda T (1994) J Biol Chem 269:30049–30055PubMedGoogle Scholar
  33. 33.
    Mosyak L, Reshetnikova L, Goldgur Y, Delarue M, Safro MG (1995) Nat Struct Biol 2:537–547PubMedCrossRefGoogle Scholar
  34. 34.
    Reshetnikova L, Moor N, Lavrik O, Vassylyev DG (1999) J Mol Biol 287:555–568PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. (outside the USA)  2012

Authors and Affiliations

  • Kemin Tan
    • 1
    • 2
    • 3
  • Min Zhou
    • 1
    • 2
  • Rongguang Zhang
    • 1
    • 2
    • 3
  • Wayne F. Anderson
    • 1
    • 4
  • Andrzej Joachimiak
    • 1
    • 2
    • 3
  1. 1.Center for Structural Genomics of Infectious DiseasesUniversity of ChicagoChicagoUSA
  2. 2.Computation InstituteUniversity of ChicagoChicagoUSA
  3. 3.Structural Biology CenterBiosciences, Argonne National LaboratoryArgonneUSA
  4. 4.Molecular Pharmacology and Biological ChemistryNorthwestern UniversityChicagoUSA

Personalised recommendations