Preferences help
enabled [disable] Abstract
Number of results
2001 | 48 | 2 | 337-350
Article title

Methionyl-tRNA synthetase.

Title variants
Languages of publication
Methionyl-tRNA synthetase (MetRS) belongs to the family of 20 enzymes essential for protein biosynthesis. It links covalently methionine with its cognate tRNA. Crystal structures solved for bacterial MetRSs have given a number of interesting insights into enzyme architecture and methionylation catalysis. A comparison of sequences of MetRSs belonging to all kingdoms of life, as well as numerous biochemical and genetic studies have revealed the presence of various additional domains appended to the catalytic core of synthetase. They are responsible for interactions with tRNA and proteins. Tertiary structure of C-terminal tRNA-binding appendices can be deduced from those determined for their homologues: tRNA binding protein 111 and endothelial monocyte-activating polypeptide II. Contacts between MetRS and other proteins could be mediated not only by noncatalytic peptides but also by structural elements present in the catalytic core, e.g. Arg-Gly-Asp (RGD) motifs. Additional activities involve MetRS in the maintenance of translational fidelity and in coordination of ribosome biogenesis with protein synthesis.

Physical description
  • Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Poznań, Poland
  • Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Poznań, Poland
  • 1. Eriani, G., Delarue, M., Poch, O., Gangloff, J. & Moras, D. (1990) Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature 347, 203-206.
  • 2. Cusack, S. (1997) Aminoacyl-tRNA synthetases. Curr. Opin. Struct. Biol. 7, 881-889.
  • 3. Arnez, J.G. & Moras, D. (1997) Structural and functional consideration of the aminoacylation reaction. Trends Biochem. Sci. 22, 211- 216.
  • 4. Cussack, S. (1999) RNA-protein complexes. Curr. Opin. Struct. Biol. 9, 66-73.
  • 5. Mechulam, Y., Schmitt, E., Maveyraud, L., Zelwer, C., Nureki, O., Yokoyama, S., Konno, M. & Blanquet, S. (1999) Crystal structure of Escherichia coli methionyl-tRNA synthetase highlights species-specific features. J. Mol. Biol. 294, 1287-1297.
  • 6. Sugiura, I., Nureki, O., Ugaji-Yoshikawa, Y., Kuwabara, S., Shimada, A., Tateno, M., Lorber, B., Giegé, R., Moras, D., Yokoyama, S. & Konno, M. (2000) The 2.0 Å crystal structure of Thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules. Structure 8, 197-208.
  • 7. Rould, M.A., Perona, J.J., Söll, D. & Steitz, T.A. (1989) Structure of E. coli glutaminyl-tRNA synthetase complexed with tRNAGln and ATP at 2.8 Å resolution. Science 246, 1135-1142.
  • 8. Fourmy, D., Mechulam, Y. & Blanquet, S. (1995) Crucial role of an idiosyncratic insertion in the Rossmann fold of class I aminoacyl-tRNA synthetases: The case of methionyl-tRNA synthetase. Biochemistry 34, 15681-15688.
  • 9. Kim, S., Joon, Jo Y., Ho, Lee S., Motegi, H., Shiba, K., Sassanfar, M. & Martinis, S. (1998) Biochemical and phylogenetic analyses of methionyl-tRNA synthetase isolated from a pathogenic microorganism, Mycobacterium tuberculosis. FEBS Lett. 427, 259-262.
  • 10. Blanquet, S., Fayat, G., Waller, J.P. & Iwatsubo, M. (1972) The mechanism of action of methionyl-tRNA synthetase from Escherichia coli - interaction with ligands of the amino- acid-activation reaction. Eur. J. Biochem. 24, 461-469.
  • 11. Blanquet, S., Iwatsubo, M. & Waller, J.P. (1973) The mechanism of action of methionyl-tRNA synthetase. Fluorescence studies on tRNAMet binding as a function of ligands, ions and pH. Eur. J. Biochem. 36, 213-226.
  • 12. Blanquet, S., Fayat, G. & Waller, J.P. (1975) The amino acid activation reaction catalyzed by methionyl-transfer RNA synthetase: Evidence for synergistic coupling between the sites for methionine, adenosine and pyrophosphate. J. Mol. Biol. 94, 1-15.
  • 13. Ghosh, G., Pelka, H. & Schulman, L.H. (1990) Identification of the tRNA anticodon recognition site of Escherichia coli methionyl-tRNA synthetase. Biochemistry 29, 2220-2225.
  • 14. Meinnel, T., Mechulam, Y., Corre, D.L., Panvert, M., Blanquet, S. & Fayat, G. (1991) Selection of suppressor methionyl-tRNA synthetases: Mapping the tRNA anticodon binding site. Proc. Natl. Acad. Sci. U.S.A. 88, 291-295.
  • 15. Ghosh, G., Kim, H.Y., Demaret, J.P., Brunie, S. & Schulman, L.H. (1991) Arginine-395 is required for efficient in vivo and in vitro aminoacylation of tRNAs by Escherichia coli methionyl-tRNA synthetase. Biochemistry 30, 11767-11774.
  • 16. Kim, H. Y., Pelka, H., Brunie, S. & Schulman, L.H. (1993) Two separate peptides in Escherichia coli methionyl-tRNA synthetase form the anticodon binding site for methionine tRNA. Biochemistry 32, 10506-10511.
  • 17. Fourmy, D., Mechulam, Y., Brunie, S., Blanquet, S. & Fayat, G. (1991) Identification of residues involved in the binding of methionine by Escherichia coli methionyl-tRNA synthetase. FEBS Lett. 292, 259-263.
  • 18. Mechulam, Y., Schmitt, E., Panvert, M., Schmitter, J.M., Lapadat-Tapolsky, M., Meinnel, T., Dessen, P., Blanquet, S. & Fayat, G. (1991) Methionyl-transfer RNA synthetase from Bacillus stearothermophilus: Structural and functional identities with the Escherichia coli enzyme. Nucleic Acids Res. 19, 3673- 3681.
  • 19. Schmitt, E., Panvert, M., Mechulam, Y. & Blanquet, S. (1997) General structure/function properties of microbial methionyl-tRNA synthetases. Eur. J. Biochem. 246, 539-547.
  • 20. Ghosh, G., Pelka, H., Schulman, L.H. & Brunie, S. (1991) Activation of methionine by Escherichia coli methionyl-tRNA synthetase. Biochemistry 30, 9569-9575.
  • 21. Brick, P. & Blow, D.M. (1987) Crystal structure of a deletion mutant of a tyrosyl-tRNA synthetase complexed with tyrosine. J. Mol. Biol. 194, 287-297.
  • 22. Alexander, R.W. & Schimmel, P. (1999) Evidence for breaking domain-domain functional communication in a synthetase-tRNA complex. Biochemistry 38, 16359-16365.
  • 23. Kamińska, M., Deniziak, M., Kerjan, P., Barciszewski, J. & Mirande, M. (2000) A recurrent RNA binding domain appended to plant methionyl-tRNA synthetase acts as cis-acting cofactor for aminoacylation. EMBO J. 19, 6908-6917.
  • 24. Cassio, D. & Waller, J.P. (1971) Modification of methionyl-tRNA synthetase by proteolytic cleavage and properties of the trypsin-modified enzyme. Eur. J. Biochem. 20, 283-300.
  • 25. Mellot, P., Mechulam, Y., LeCorre, D., Blanquet, S. & Fayat, G. (1989) Identification of an amino acid region supporting specific methionyl-tRNA synthetase: tRNA recognition. J. Mol. Biol. 208, 429-443.
  • 26. Quevillon, S., Agou, F., Robinson, J.C. & Mirande, M. (1997) The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyte-activating polypeptide II cytokine. J. Biol. Chem. 272, 32573-32579.
  • 27. Morales, A.J., Swairjo, M.A. & Schimmel, P. (1999) Structure-specific tRNA-binding protein from the extreme thermophile Aquifex aeolicus. EMBO J. 18, 3475-3483.
  • 28. Kao, J., Ryan, J., Brett, G., Chen, J., Shen, H., Fan, Y.G., Godman, G., Familletti, P.C., Wang, F., Pan, Y.C. E., Stern, D. & Clauss, M. (1992) Endothelial monocyte-activating polypeptide II. J. Biol. Chem. 267, 20239-20247.
  • 29. Kao, J., Fan, Y.G., Haehnel, I., Brett, J., Greenberg, S., Clauss, M., Kayton, M., Houck, K., Kisiel, W., Seljelid, R., Burnier, J. & Stern, D. (1994) A peptide derived from the amino terminus of endothelial-monocyte-activating polypeptide II modulates mononuclear and polymorphonuclear leukocyte functions, defines an apparently novel cellular interaction site, and induces an acute inflammatory response. J. Biol. Chem. 269, 9774-9782.
  • 30. Kao, J., Houck, K., Fan, Y., Haehnel, I., Libutti, S.K., Kayton, M., Grikscheit, T., Chabot, J., Nowygrod, R., Greenberg, S., Kuang, W.J., Leung, D.W., Hayward, J.R., Kisiel, W., Heath, M., Brett, J. & Stern, D.M. (1994) Characterization of a novel tumor-derived cytokine. J. Biol. Chem. 269, 25106- 25119.
  • 31. Tas, M.P.R. & Murray, J.C. (1996) Endothelial-monocyte-activating polypeptide II. Int. J. Biochem. Cell Biol. 28, 837-841.
  • 32. Wakasugi, K. & Schimmel, P. (1999) Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science 284, 147-150.
  • 33. Swairjo, M.A., Morales, A.J., Wang, C.C., Ortiz, A.R. & Schimmel, P. (2000) Crystal structure of Trbp111: A structure-specific tRNA-binding protein. EMBO J. 19, 6287- 6298.
  • 34. Kim, Y., Shin, J., Li, R., Cheong, C., Kim, K. & Kim, S. (2000) A novel anti-tumor cytokine contains an RNA binding motif present in aminoacyl-tRNA synthetases. J. Biol. Chem. 275, 27062-27068.
  • 35. Ruff, M., Krishnaswamy, S., Boeglin, M., Poterszman, A., Mitschler, A., Podjarny, A., Rees, B., Thierry, J.C. & Moras, D. (1991) Class II aminoacyl transfer RNA synthetases: Crystal structure of yeast aspartyl-tRNA synthetase complexed with tRNAAsp. Science 252, 1682-1689.
  • 36. Commans, S., Plateau, P., Blanquet, S. & Dardel, F. (1995) Solution structure of the anticodon-binding domain of Escherichia coli lysyl-tRNA synthetase and studies of its interaction with tRNALys. J. Mol. Biol. 253, 100-113.
  • 37. Berthet-Colominas, C., Seignovert, L., Hartlein, M., Grotli, M., Cusack, S. & Leberman, R. (1998) The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate: The mechanism of discrimination between asparagine and aspartic acid. EMBO J. 17, 2947-2960.
  • 38. Goldgur, Y., Mosyak, L., Reshetnikova, L., Ankilova, V., Lavrik, O., Khodyreva, S. & Safro, M. (1997) The crystal structure of phenylalanyl-tRNA synthetase from Thermus thermophilus complexed with cognate tRNAPhe. Structure 5, 59-68.
  • 39. Lage, H. & Dietel, M. (1996) Cloning of a human cDNA encoding a protein with high homology to yeast methionyl-tRNA synthetase. Gene 178, 187-189.
  • 40. Rho, S.B., Kim, M.J., Lee, J.S., Seol, W., Motegi, H., Kim, S. & Shiba, K. (1999) Genetic dissection of protein-protein interactions in multi-tRNA synthetase complex. Proc. Natl. Acad. Sci. U.S.A. 96, 4488-4493.
  • 41. Berthonneau, E. & Mirande, M. (2000) A gene fusion event in the evolution of aminoacyl-tRNA synthetases. FEBS Lett. 470, 300- 304.
  • 42. Simos, G., Segref, A., Fasiolo, F., Hellmuth, K., Shevchenko, A., Mann, M. & Hurt, E.C. (1996) The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyl- and glutamyl-tRNA synthetases. EMBO J. 15, 5437-5448.
  • 43. Simos, G., Sauer, A., Fasiolo, F. & Hurt, E.C. (1998) A conserved domain within Arc1p delivers tRNA to aminoacyl-tRNA synthetases. Mol. Cell 1, 235-242.
  • 44. Mirande, M. (1991) Aminoacyl-tRNA synthetase family from prokaryotes and eukaryotes: Structural domains and their implications. Prog. Nucleic Acid Res. Mol. Biol. 40, 95-142.
  • 45. Kisselev, L.L. & Wolfson, A.D. (1994) Aminoacyl-tRNA synthetase from higher eukaryotes. Prog. Nucleic Acid Res. Mol. Biol. 48, 83-142.
  • 46. Yang, D.C.H. (1996) Mammalian aminoacyl- tRNA synthetases. Curr. Top. Cell. Regul. 34, 101-136.
  • 47. Quevillon, S., Robinson, J.C., Berthonneau, E., Siatecka, M. & Mirande, M. (1999) Macromolecular assemblage of aminoacyl-tRNA synthetases: Identification of protein-protein interactions and characterization of a core protein. J. Mol. Biol. 285, 183-195.
  • 48. Norcum, M.T. & Warrington, A. (1998) Structural analysis of the multienzyme aminoacyl-tRNA synthetase complex: A three-domain model based on reversible chemical crosslinking. Protein Sci. 7, 79-87.
  • 49. Pierschbacher, M.D. & Rouslahti, E. (1984) Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 309, 30-33.
  • 50. Suzuki, S., Oldberg, A., Hayman, E.G., Pierschbacher, M.D. & Rouslahti, E. (1985) Complete amino acid sequence of human vitronectin deduced from cDNA. Similarity of cell attachment sites in vitronectin and fibronectin. EMBO J. 4, 2519-2524.
  • 51. Watt, K.W.K., Cottrall, B.A., Strong, D.D. & Doolittle, R.F. (1979) Amino acid sequence studies on the alpha chain of human fibrinogen. Overlapping sequences providing the complete sequence. Biochemistry 18, 5410-5416.
  • 52. Plow, E.F., Haas, T.A., Zhang, L., Loftus, J. & Smith, J.W. (2000) Ligand binding to integrins. J. Biol. Chem. 275, 21785-21788.
  • 53. Martinis, S.A., Plateau, P., Cavarelli, J. & Florentz, C. (1999) Aminoacyl-tRNA synthetases: A family of expanding functions. EMBO J. 18, 4591-4596.
  • 54. Jakubowski, H., Zhang, L., Bardeguez, A. & Aviv, A. (2000) Homocysteine thiolactone and protein homocysteinylation in human endothelial cells. Implications for atherosclerosis. Circ. Res. 87, 45-51.
  • 55. Jakubowski, H. (1995) Proofreading in vivo. Editing of homocysteine by aminoacyl-tRNA synthetases in Escherichia coli. J. Biol. Chem. 270, 17672-17673.
  • 56. Jakubowski, H. & Fersht, A.R. (1981) Alternative pathways for editing non-cognate amino acids by aminoacyl-tRNA synthetases. Nucleic Acids Res. 9, 3105-3117.
  • 57. Fersht, A. R. & Dingwall, C. (1979) An editing mechanism for the methionyl-tRNA synthetase in the selection of amino acids in protein synthesis. Biochemistry 18, 1250-1256.
  • 58. Jakubowski, H. (2000) Translational incorporation of S-nitrosohomocysteine into protein. J. Biol. Chem. 275, 21813-21816.
  • 59. Nathanson, L. & Deutscher, M.P. (2000) Active aminoacyl-tRNA synthetases are present in nuclei as a high molecular weight multienzyme complex. J. Biol. Chem. 275, 31559- 31562.
  • 60. Ko, Y.G., Kang, Y.S., Kim, E.K., Park, S.G. & Kim, S. (2000) Nucleolar localization of human methionyl-tRNA synthetase and its role in ribosomal RNA synthesis. J. Cell Biol. 149, 567-574.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.