Biopolym. Cell. 1998; 14(4):349-359.
http://dx.doi.org/10.7124/bc.0004DF
Structural and functional investigation of mammalian tyrosyl-tRNA synthetase
1Kornelyuk A. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

The main results of the structural and functional investigation of mammalian tyrosyl-tRNA synthetase are reviewed. The multiplicity of molecular forms of enzyme is analyzed. Structure of the active site of synthetase has been studied by chemical modification methods and the essential, role of lysine, histidine and cysteine residues has been revealed. It was found that the anticodon of homologous bovine tRNATyr is involved in the interaction with the main form of synthetase in the complex. Conformational changes of enzyme in the course of substrate binding, including tRNA recognition have been revealed. On the basis of the data obtained the dynamical model of functioning of tyrosyl-tRNA synthetase has been proposed. Primary structure of bovine tyrosyl-tRNA synthetase has been determined by cDNA cloning and sequencing. The modular organization of tyrosyl-tRNA synthetase is proposed where the catalytic part of enzyme composed by Rossniann fold and α-helical domain is connected to a cytokine-like C-terminaf module. The hypothesis is forwarded about possible forming of the isolated C-domain as a result of the proteolytic digestion after proiease activation and about possible cytokine like activity of this C-domain similar EMAP II cytokine.
Full text: (PDF, in Russian)

References

[1] Kisselev LL, Favorova OO, Lavrik OI. Biosynthesis of proteins from amino acids to aminoacyl-tRNA. Moscow, Nauka, 1984; 408 p.
[2] Schimmel P. Aminoacyl tRNA synthetases: general scheme of structure-function relationships in the polypeptides and recognition of transfer RNAs. Annu Rev Biochem. 1987;56:125-58. Review.
[3] Mirande M. Aminoacyl-tRNA synthetase family from prokaryotes and eukaryotes: structural domains and their implications. Prog Nucleic Acid Res Mol Biol. 1991;40:95-142.
[4] Kisselev LL, Wolfson AD. Aminoacyl-tRNA synthetases from higher eukaryotes. Prog Nucleic Acid Res Mol Biol. 1994;48:83-142.
[5] Akins RA, Lambowitz AM. A protein required for splicing group I introns in Neurospora mitochondria is mitochondrial tyrosyl-tRNA synthetase or a derivative thereof. Cell. 1987;50(3):331-45.
[6] Schray B, Knippers R. Binding of human glutaminyl-tRNA synthetase to a specific site of its mRNA. Nucleic Acids Res. 1991;19(19):5307-12.
[7] Messenguy F, Delforge J. Role of transfer ribonucleic acids in the regulation of several biosyntheses in Saccharomyces cerevisiae. Eur J Biochem. 1976;67(2):335-9.
[8] Rapaport E, Zamecnik PC, Baril EF. HeLa cell DNA polymerase alpha is tightly associated with tryptophanyl-tRNA synthetase and diadenosine 5',5"'-P1,P4-tetraphosphate binding activities. Proc Natl Acad Sci U S A. 1981;78(2):838-42.
[9] Mathews MB, Bernstein RM. Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Nature. 1983 Jul 14-20;304(5922):177-9.
[10] Vartanian OA. [Detection of autoantibodies against phenylalanyl-, tyrosyl-, and tryptophanyl-tRNA-synthetase and anti-idiotypic antibodies to it in serum from patients with autoimmune diseases]. Mol Biol (Mosk). 1991;25(4):1033-9.
[11] Korneliuk AI, Kurochkin IV, Matsuka GKh. [Tyrosyl-tRNA synthetase from the bovine liver. Isolation and physico-chemical properties]. Mol Biol (Mosk). 1988;22(1):176-86.
[12] Gnatenko DV, Korneliuk AI, Kurochkin IV, Ribkinska TA, Matsuka GKh. [Isolation and characteristics of functionally active proteolytically modified forms of tyrosyl-tRNA synthetase from bovine liver]. Ukr Biokhim Zh. 1991;63(4):61-7.
[13] Kurochkin IV, Korneliuk AI, Matsuka GKh. [Interaction of eukaryotic tyrosyl-tRNA-synthetase with high molecular weight RNA]. Mol Biol (Mosk). 1991;25(3):779-86.
[14] Gnatenko DV, Kornelyuk AI, Kurochkin IV, Matsuka GH. High molecular weight complex of tyrosyl-tRNA synthetase from bovine liver. Biopolym Cell. 1991; 7(1):63-9.
[15] Kornelyuk AI. Structural and functional studies of eukaryotic tyrosyl-tRNA synthetase: Thesis. ... dr biol. nauk. Kiev, 1995; 242 p.
[16] Ryazanov AI, Spirin AS. Compartmentalization of biochemical processes in the polyribosomes and other subcellular structures. Usp biol khim. 1988; 29:3-43.
[17] Spirin AS, Ovchinnikov LP Compartmentalization of proteins in eukaryotic translation apparatus on polyribosomes. Prospects bioorgan, chemistry and molecular. biology. Nauka, 1986:59-67.
[18] Alzhanova AT, Fedorov AN, Ovchinnikov LP, Spirin AS. Eukaryotic aminoacyl-tRNA synthetases are RNA-binding proteins whereas prokaryotic ones are not. FEBS Lett. 1980;120(2):225-9.
[19] Ribkinska TA, Vartanyan OA, Filonenko VV, Sidorik LL, Kornelyuk AI, Beresten SF. A method for selection of hybridomas, secreting monoclonal antibodies against tyrosyl-tRNA synthetase, based on monitoring of the enzymatic activity. Biopolym Cell. 1990; 6(4):97-101.
[20] Ribkinska TA, Kornelyuk AI, Beresten SF, Matsuka GKh. The immunochemical approach for studies of structure tyrosyl-tRNA synthetase from bovine liver. Biopolym Cell. 1991; 7(5):33-6.
[21] Rozhko OT, Korneliuk AI, Ribkhinska TA, Savinskaia LN, Odynets KA, Matsuka GKh. [Production of polyclonal antibodies to tyrosyl-tRNA-synthetase from the bovine liver and characterization of two forms of the enzyme]. Ukr Biokhim Zh. 1997;69(3):9-16.
[22] Gnatenko DV, Korneliuk AI, Matsuka GKh. [Tyrosyl-tRNA-synthetase from bovine liver. Functional role of histidine residues]. Bioorg Khim. 1991;17(8):1033-7.
[23] Fersht AR, Knill-Jones JW, Bedouelle H, Winter G. Reconstruction by site-directed mutagenesis of the transition state for the activation of tyrosine by the tyrosyl-tRNA synthetase: a mobile loop envelopes the transition state in an induced-fit mechanism. Biochemistry. 1988;27(5):1581-7.
[24] Gnatenko DV, Kornelyuk AI, Matsuka GKh. Studies in the functional role of lysine residues of tyrosyl-tRNA synthetase from the bovine liver by the method of chemical modification with o-phthalaldehyde. Doklady Akad Nauk Ukr SSR. 1991;(5):140-3.
[25] Gnatenko DV, Korneliuk AI, Lavrik OI. [Chemical modification of lysine residues in tyrosyl-tRNA-synthetase from cattle liver using pyridoxal-5'-phosphate]. Biokhimiia. 1991;56(11):1984-90.
[26] Gnatenko DV, Korneiyuk A, Matsuka GKh. One lysine residue of tyrosyl-tRNA synthetase from bovine liver is critical for aminoacylation of tRNATyr. Abstrs of 21th FEBS Meet. Dublin, 1992. Suppl. Tu:l80.
[27] Bedouelle H. Recognition of tRNA(Tyr) by tyrosyl-tRNA synthetase. Biochimie. 1990;72(8):589-98.
[28] Kalachniuk LH, Korneliuk OI, Matsuka HKh. [Tyrosine tRNA(Q*psiA) from bovine liver. Identification of its sites of interaction with homologous aminoacyl-trna synthetase using chemical modification]. Ukr Biokhim Zh. 1995;67(5):60-5.
[29] Schimmel P, Gieg? R, Moras D, Yokoyama S. An operational RNA code for amino acids and possible relationship to genetic code. Proc Natl Acad Sci U S A. 1993;90(19):8763-8.
[30] Klimenko IV, Kornelyuk AI, Matsuka GKh. Conformational change of tyrosyl-tRNA synthetase from bovine liver in the course of cognate tRNA binding revealed from fluorescence spectroscopy data. Biopolym Cell. 1993; 9(6):31-5.
[31] Kornelyuk AI, Klimenko IV, Odynets KA. Conformational change of mammalian tyrosyl-tRNA synthetase induced by tyrosyl adenylate formation. Biochem Mol Biol Int. 1995;35(2):317-22.
[32] Perona JJ, Rould MA, Steitz TA. Structural basis for transfer RNA aminoacylation by Escherichia coli glutaminyl-tRNA synthetase. Biochemistry. 1993;32(34):8758-71.
[33] Careri G. The fluctuating enzyme. Quantum statistical mechanics in the natural sciences. New York; London, 1974: 15-35.
[34] Demchenko AP. [Equilibrium intramolecular mobility in proteins]. Ukr Biokhim Zh. 1981;53(4):114-28.
[35] Demchenko AP. Luminescence and dynamics of proteins structure. Kyiv, Naukova Dumka, 1988; 280 p
[36] Guscha TO, Klimenko IV, Kornelyuk AI. Nanosecond conformational mobility tyrosyl-tRNK synthetase in solution according to the tryptophan fluorescence quenching. Doklady Akad Nauk Ukr SSR. Ser B. 1990; (7):77-80.
[37] Klimenko IV, Guscha TO, Kornelyuk AI. Properties of tryptophan fluorescence of two forms of tyrosyl-tRNA synthetase from bovine liver. Biopolym Cell. 1991; 7(6):83-8.
[38] Gnatenko DK, Klimenko IV, Korneiyuk AI, Odynets KA. Conformation fluctuations of mammalian tyrosyl-tRNA synthetase in solution studied by fluorescence spectroscopy. Abstrs of 22nd Meet, of the FEBS. Stockholm, 1993: 190.
[39] Kornelyuk OI. Structural and dynamchiyia model of eukaryotic tyrosyl-tRNA synthetase. Abstracts reported. II Congress of Ukrainian Biophysical Society. Kharkiv, 1998: 40.
[40] Levanets OV, Naidenov VG, Woodmaska MI, Odynets KA, Matsuka GH, Kornelyuk AI. PCR amplification, cloning and sequencing of cDNA fragment encoding a nucleotide binding domain of mammalian tyrosyl-tRNA synthetase Biopolym Cell. 1996; 12(5):66-71.
[41] Levanets OV, Naidenov VG, Woodmaska MI, Matsuka GH, Kornelyuk AI. Cloning of cDNA encoding C-terminal part of mammalian tyrosyl-tRNA synthetase using of PCR-amplified radioactive probe. Biopolym. Cell. 1997; 13(2):121-6
[42] Levanets OV, Naidenov VG, Odynets KA, Woodmaska MI, Matsuka GKh, Kornelyuk AI. Homology of C-terminal non-catalytic domain of mammalian tyrosyl-tRNA synthetase with cylokine EMAP II and non-catalytic domains of methionyl- and phenylalanyl-tRNA synthetases. Biopolym Cell. 1997; 13(6):474-8
[43] Kao J, Ryan J, Brett G, Chen J, Shen H, Fan YG, Godman G, Familletti PC, Wang F, Pan YC, et al. Endothelial monocyte-activating polypeptide II. A novel tumor-derived polypeptide that activates host-response mechanisms. J Biol Chem. 1992;267(28):20239-47.
[44] Kao J, Houck K, Fan Y, Haehnel I, Libutti SK, Kayton ML, Grikscheit T, Chabot J, Nowygrod R, Greenberg S, et al. Characterization of a novel tumor-derived cytokine. Endothelial-monocyte activating polypeptide II. J Biol Chem. 1994;269(40):25106-19.
[45] Tas MP, Murray JC. Endothelial-monocyte-activating polypeptide II. Int J Biochem Cell Biol. 1996;28(8):837-41.
[46] Wilson R, Ainscough R, Anderson K, Baynes C, Berks M, Bonfield J, Burton J, Connell M, Copsey T, Cooper J, et al. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature. 1994;368(6466):32-8.
[47] Simos G, Segref A, Fasiolo F, Hellmuth K, Shevchenko A, Mann M, Hurt EC. The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyl- and glutamyl-tRNA synthetases. EMBO J. 1996;15(19):5437-48.
[48] Quevillon S, Agou F, Robinson JC, Mirande M. 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. 1997;272(51):32573-9.
[49] Cassio D, Waller JP. Modification of methionyl-tRNA synthetase by proteolytic cleavage and properties of the trypsin-modified enzyme. Eur J Biochem. 1971;20(2):283-300.
[50] Goldgur Y, Mosyak L, Reshetnikova L, Ankilova V, Lavrik O, Khodyreva S, Safro M. The crystal structure of phenylalanyl-tRNA synthetase from thermus thermophilus complexed with cognate tRNAPhe. Structure. 1997;5(1):59-68.
[51] Pathak VK, Nielsen PJ, Trachsel H, Hershey JW. Structure of the beta subunit of translational initiation factor eIF-2. Cell. 1988;54(5):633-9.
[52] Kleeman TA, Wei D, Simpson KL, First EA. Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine. J Biol Chem. 1997;272(22):14420-5.
[53] Rogers S, Wells R, Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986;234(4774):364-8.
[54] Jacobo-Molina A, Villa-Garcia M, Chen HC, Yang DC. Proteolytic signal sequences (PEST) in the mammalian aminoacyl-tRNA synthetase complex. FEBS Lett. 1988;232(1):65-8.