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. 1995 Sep 1;14(17):4143–4155. doi: 10.1002/j.1460-2075.1995.tb00088.x

Crystal structure of histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate.

J G Arnez 1, D C Harris 1, A Mitschler 1, B Rees 1, C S Francklyn 1, D Moras 1
PMCID: PMC394497  PMID: 7556055

Abstract

The crystal structure at 2.6 A of the histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate has been determined. The enzyme is a homodimer with a molecular weight of 94 kDa and belongs to the class II of aminoacyl-tRNA synthetases (aaRS). The asymmetric unit is composed of two homodimers. Each monomer consists of two domains. The N-terminal catalytic core domain contains a six-stranded antiparallel beta-sheet sitting on two alpha-helices, which can be superposed with the catalytic domains of yeast AspRS, and GlyRS and SerRS from Thermus thermophilus with a root-mean-square difference on the C alpha atoms of 1.7-1.9 A. The active sites of all four monomers are occupied by histidyl-adenylate, which apparently forms during crystallization. The 100 residue C-terminal alpha/beta domain resembles half of a beta-barrel, and provides an independent domain oriented to contact the anticodon stem and part of the anticodon loop of tRNA(His). The modular domain organization of histidyl-tRNA synthetase reiterates a repeated theme in aaRS, and its structure should provide insight into the ability of certain aaRS to aminoacylate minihelices and other non-tRNA molecules.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amaar Y. G., Baillie D. L. Cloning and characterization of the C.elegans histidyl-tRNA synthetase gene. Nucleic Acids Res. 1993 Dec 25;21(25):6050–6051. [PMC free article] [PubMed] [Google Scholar]
  2. Belrhali H., Yaremchuk A., Tukalo M., Larsen K., Berthet-Colominas C., Leberman R., Beijer B., Sproat B., Als-Nielsen J., Grübel G. Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate. Science. 1994 Mar 11;263(5152):1432–1436. doi: 10.1126/science.8128224. [DOI] [PubMed] [Google Scholar]
  3. Biou V., Yaremchuk A., Tukalo M., Cusack S. The 2.9 A crystal structure of T. thermophilus seryl-tRNA synthetase complexed with tRNA(Ser). Science. 1994 Mar 11;263(5152):1404–1410. doi: 10.1126/science.8128220. [DOI] [PubMed] [Google Scholar]
  4. Brick P., Bhat T. N., Blow D. M. Structure of tyrosyl-tRNA synthetase refined at 2.3 A resolution. Interaction of the enzyme with the tyrosyl adenylate intermediate. J Mol Biol. 1989 Jul 5;208(1):83–98. doi: 10.1016/0022-2836(89)90090-9. [DOI] [PubMed] [Google Scholar]
  5. Brunie S., Zelwer C., Risler J. L. Crystallographic study at 2.5 A resolution of the interaction of methionyl-tRNA synthetase from Escherichia coli with ATP. J Mol Biol. 1990 Nov 20;216(2):411–424. doi: 10.1016/S0022-2836(05)80331-6. [DOI] [PubMed] [Google Scholar]
  6. Brünger A. T., Kuriyan J., Karplus M. Crystallographic R factor refinement by molecular dynamics. Science. 1987 Jan 23;235(4787):458–460. doi: 10.1126/science.235.4787.458. [DOI] [PubMed] [Google Scholar]
  7. Cavarelli J., Eriani G., Rees B., Ruff M., Boeglin M., Mitschler A., Martin F., Gangloff J., Thierry J. C., Moras D. The active site of yeast aspartyl-tRNA synthetase: structural and functional aspects of the aminoacylation reaction. EMBO J. 1994 Jan 15;13(2):327–337. doi: 10.1002/j.1460-2075.1994.tb06265.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cavarelli J., Rees B., Ruff M., Thierry J. C., Moras D. Yeast tRNA(Asp) recognition by its cognate class II aminoacyl-tRNA synthetase. Nature. 1993 Mar 11;362(6416):181–184. doi: 10.1038/362181a0. [DOI] [PubMed] [Google Scholar]
  9. Cerini C., Kerjan P., Astier M., Gratecos D., Mirande M., Sémériva M. A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase. EMBO J. 1991 Dec;10(13):4267–4277. doi: 10.1002/j.1460-2075.1991.tb05005.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cusack S., Berthet-Colominas C., Härtlein M., Nassar N., Leberman R. A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A. Nature. 1990 Sep 20;347(6290):249–255. doi: 10.1038/347249a0. [DOI] [PubMed] [Google Scholar]
  11. Cusack S., Härtlein M., Leberman R. Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases. Nucleic Acids Res. 1991 Jul 11;19(13):3489–3498. doi: 10.1093/nar/19.13.3489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Delarue M., Moras D. The aminoacyl-tRNA synthetase family: modules at work. Bioessays. 1993 Oct;15(10):675–687. doi: 10.1002/bies.950151007. [DOI] [PubMed] [Google Scholar]
  13. Doublié S., Bricogne G., Gilmore C., Carter C. W., Jr Tryptophanyl-tRNA synthetase crystal structure reveals an unexpected homology to tyrosyl-tRNA synthetase. Structure. 1995 Jan 15;3(1):17–31. doi: 10.1016/s0969-2126(01)00132-0. [DOI] [PubMed] [Google Scholar]
  14. Eriani G., Delarue M., Poch O., Gangloff J., Moras D. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature. 1990 Sep 13;347(6289):203–206. doi: 10.1038/347203a0. [DOI] [PubMed] [Google Scholar]
  15. Fett R., Knippers R. The primary structure of human glutaminyl-tRNA synthetase. A highly conserved core, amino acid repeat regions, and homologies with translation elongation factors. J Biol Chem. 1991 Jan 25;266(3):1448–1455. [PubMed] [Google Scholar]
  16. Francklyn C., Harris D., Moras D. Crystallization of histidyl-tRNA synthetase from Escherichia coli. J Mol Biol. 1994 Aug 12;241(2):275–277. doi: 10.1006/jmbi.1994.1498. [DOI] [PubMed] [Google Scholar]
  17. Francklyn C., Schimmel P. Enzymatic aminoacylation of an eight-base-pair microhelix with histidine. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8655–8659. doi: 10.1073/pnas.87.21.8655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Francklyn C., Shi J. P., Schimmel P. Overlapping nucleotide determinants for specific aminoacylation of RNA microhelices. Science. 1992 Feb 28;255(5048):1121–1125. doi: 10.1126/science.1546312. [DOI] [PubMed] [Google Scholar]
  19. Freedman R., Gibson B., Donovan D., Biemann K., Eisenbeis S., Parker J., Schimmel P. Primary structure of histidine-tRNA synthetase and characterization of hisS transcripts. J Biol Chem. 1985 Aug 25;260(18):10063–10068. [PubMed] [Google Scholar]
  20. Giegé R., Puglisi J. D., Florentz C. tRNA structure and aminoacylation efficiency. Prog Nucleic Acid Res Mol Biol. 1993;45:129–206. doi: 10.1016/s0079-6603(08)60869-7. [DOI] [PubMed] [Google Scholar]
  21. Himeno H., Hasegawa T., Ueda T., Watanabe K., Miura K., Shimizu M. Role of the extra G-C pair at the end of the acceptor stem of tRNA(His) in aminoacylation. Nucleic Acids Res. 1989 Oct 11;17(19):7855–7863. doi: 10.1093/nar/17.19.7855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hingerty B., Brown R. S., Jack A. Further refinement of the structure of yeast tRNAPhe. J Mol Biol. 1978 Sep 25;124(3):523–534. doi: 10.1016/0022-2836(78)90185-7. [DOI] [PubMed] [Google Scholar]
  23. Jones T. A., Zou J. Y., Cowan S. W., Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991 Mar 1;47(Pt 2):110–119. doi: 10.1107/s0108767390010224. [DOI] [PubMed] [Google Scholar]
  24. Logan D. T., Mazauric M. H., Kern D., Moras D. Crystal structure of glycyl-tRNA synthetase from Thermus thermophilus. EMBO J. 1995 Sep 1;14(17):4156–4167. doi: 10.1002/j.1460-2075.1995.tb00089.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Menguito C. A., Keherly M. J., Tang C., Papaconstantinou J., Weigel P. H. Molecular cloning, sequence, structural analysis and expression of the histidyl-tRNA synthetase gene from Streptococcus equisimilis. Nucleic Acids Res. 1993 Feb 11;21(3):615–620. doi: 10.1093/nar/21.3.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Natsoulis G., Hilger F., Fink G. R. The HTS1 gene encodes both the cytoplasmic and mitochondrial histidine tRNA synthetases of S. cerevisiae. Cell. 1986 Jul 18;46(2):235–243. doi: 10.1016/0092-8674(86)90740-3. [DOI] [PubMed] [Google Scholar]
  27. Nicholls A., Sharp K. A., Honig B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins. 1991;11(4):281–296. doi: 10.1002/prot.340110407. [DOI] [PubMed] [Google Scholar]
  28. Onesti S., Miller A. D., Brick P. The crystal structure of the lysyl-tRNA synthetase (LysU) from Escherichia coli. Structure. 1995 Feb 15;3(2):163–176. doi: 10.1016/s0969-2126(01)00147-2. [DOI] [PubMed] [Google Scholar]
  29. Poterszman A., Delarue M., Thierry J. C., Moras D. Synthesis and recognition of aspartyl-adenylate by Thermus thermophilus aspartyl-tRNA synthetase. J Mol Biol. 1994 Nov 25;244(2):158–167. doi: 10.1006/jmbi.1994.1716. [DOI] [PubMed] [Google Scholar]
  30. Quigley G. J., Rich A. Structural domains of transfer RNA molecules. Science. 1976 Nov 19;194(4267):796–806. doi: 10.1126/science.790568. [DOI] [PubMed] [Google Scholar]
  31. Raben N., Borriello F., Amin J., Horwitz R., Fraser D., Plotz P. Human histidyl-tRNA synthetase: recognition of amino acid signature regions in class 2a aminoacyl-tRNA synthetases. Nucleic Acids Res. 1992 Mar 11;20(5):1075–1081. doi: 10.1093/nar/20.5.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Raben N., Nichols R., Dohlman J., McPhie P., Sridhar V., Hyde C., Leff R., Plotz P. A motif in human histidyl-tRNA synthetase which is shared among several aminoacyl-tRNA synthetases is a coiled-coil that is essential for enzymatic activity and contains the major autoantigenic epitope. J Biol Chem. 1994 Sep 30;269(39):24277–24283. [PubMed] [Google Scholar]
  33. Rees B., Bilwes A., Samama J. P., Moras D. Cardiotoxin VII4 from Naja mossambica mossambica. The refined crystal structure. J Mol Biol. 1990 Jul 5;214(1):281–297. doi: 10.1016/0022-2836(90)90161-e. [DOI] [PubMed] [Google Scholar]
  34. Rould M. A., Perona J. J., Steitz T. A. Structural basis of anticodon loop recognition by glutaminyl-tRNA synthetase. Nature. 1991 Jul 18;352(6332):213–218. doi: 10.1038/352213a0. [DOI] [PubMed] [Google Scholar]
  35. Ruff M., Krishnaswamy S., Boeglin M., Poterszman A., Mitschler A., Podjarny A., Rees B., Thierry J. C., Moras D. Class II aminoacyl transfer RNA synthetases: crystal structure of yeast aspartyl-tRNA synthetase complexed with tRNA(Asp). Science. 1991 Jun 21;252(5013):1682–1689. doi: 10.1126/science.2047877. [DOI] [PubMed] [Google Scholar]
  36. Springer M., Graffe M., Dondon J., Grunberg-Manago M. tRNA-like structures and gene regulation at the translational level: a case of molecular mimicry in Escherichia coli. EMBO J. 1989 Aug;8(8):2417–2424. doi: 10.1002/j.1460-2075.1989.tb08372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sussman J. L., Holbrook S. R., Warrant R. W., Church G. M., Kim S. H. Crystal structure of yeast phenylalanine transfer RNA. I. Crystallographic refinement. J Mol Biol. 1978 Aug 25;123(4):607–630. doi: 10.1016/0022-2836(78)90209-7. [DOI] [PubMed] [Google Scholar]
  38. Ting S. M., Bogner P., Dignam J. D. Isolation of prolyl-tRNA synthetase as a free form and as a form associated with glutamyl-tRNA synthetase. J Biol Chem. 1992 Sep 5;267(25):17701–17709. [PubMed] [Google Scholar]
  39. Wek R. C., Jackson B. M., Hinnebusch A. G. Juxtaposition of domains homologous to protein kinases and histidyl-tRNA synthetases in GCN2 protein suggests a mechanism for coupling GCN4 expression to amino acid availability. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4579–4583. doi: 10.1073/pnas.86.12.4579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yan W., Francklyn C. Cytosine 73 is a discriminator nucleotide in vivo for histidyl-tRNA in Escherichia coli. J Biol Chem. 1994 Apr 1;269(13):10022–10027. [PubMed] [Google Scholar]

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