Biopolym. Cell. 2006; 22(6):433-438.
http://dx.doi.org/10.7124/bc.000749
Structure and Function of Biopolymers
Conformational flexibility of interdomain linker in bovine tyrosyl-tRNA synthetase studied by molecular dynamics simulation
1Pydiura N. A., 1Tereshchenko F. A., 1Kornelyuk A. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

Here we report a study of molecular dynamics of a YCD2 fragment of mammalian tyrosyl-tRNA synthethase (Asp322-Ser528), which includes the COOH-terminal cytokine-like domain, intermodular flexible linker, and H5-α-helix of catalytic core of synthetase. Our calculations show that while compact C-terminal domain was less flexible and relatively stable, the interdomain linker shows a high degree of conformational changes. After short relaxation time it forms a short helix-like structure, which may be involved in the regulation of domain interaction and modulation of protein activities.
Keywords: Tyrosyl-tRNA synthetase, cytokine, C-module, molecular dynamics, linker flexibility
Full text: (PDF, in English)

References

[1] Kornelyuk AI. Structural and functional investigation of mammalian tyrosyl-tRNA synthetase. Biopolym. Cell. 1998; 14(4):349-59.
[2] 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. .
[3] 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.
[4] Bedouelle H. Recognition of tRNA(Tyr) by tyrosyl-tRNA synthetase. Biochimie. 1990;72(8):589-98. Review.
[5] Golub AG, Odynets KA, Nyporko AYu, Konelyuk AI. Structure modeling of the COOH-terminal cytokine-like module of the mammalian cytoplasmic tyrosyl-tRNA synthetase. Biopolym Cell. 2000; 16(6):515-24.
[6] 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.
[7] 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.
[8] 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.
[9] Tas MP, Murray JC. Endothelial-monocyte-activating polypeptide II. Int J Biochem Cell Biol. 1996;28(8):837-41.
[10] 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.
[11] Park SG, Jung KH, Lee JS, Jo YJ, Motegi H, Kim S, Shiba K. Precursor of pro-apoptotic cytokine modulates aminoacylation activity of tRNA synthetase. J Biol Chem. 1999;274(24):16673-6.
[12] Kornelyuk AI, Tas MPR, Dubrovsky AL, Murray JC. Cytokine activity of the non-catalytic EMAP-2-like domain of mammalian tyrosyl-tRNA synthetase. Biopolym Cell. 1999; 15(2):168-72.
[13] Wakasugi K, Schimmel P. Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science. 1999;284(5411):147-51.
[14] Wakasugi K, Schimmel P. Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase. J Biol Chem. 1999;274(33):23155-9.
[15] Simos G, Sauer A, Fasiolo F, Hurt EC. A conserved domain within Arc1p delivers tRNA to aminoacyl-tRNA synthetases. Mol Cell. 1998;1(2):235-42.
[16] Tan M, Heckmann K, Br?nen-Nieweler C. The micronuclear gene encoding a putative aminoacyl-tRNA synthetase cofactor of the ciliate Euplotes octocarinatus is interrupted by two sequences that are removed during macronuclear development. Gene. 1999;233(1-2):131-40.
[17] 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.
[18] 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.
[19] 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.
[20] Wriggers W, Chakravarty S, Jennings PA. Control of protein functional dynamics by peptide linkers. Biopolymers. 2005;80(6):736-46.
[21] 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.
[22] 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.
[23] Elofsson A, Fischer D, Rice DW, Le Grand SM, Eisenberg D. A study of combined structure/sequence profiles. Fold Des. 1996;1(6):451-61.
[24] Odynets KA, Bazylevskyi OE, Kornelyuk AI. Homology modeling of structure of NH2-terminal module of mammalian (Bos taurus) tyrosyl-tRNA synthetase. Biopolym Cell. 2002; 18(6):547-50.
[25] Lindhal E, Hess B, van der Spoel D. Gromacs 3.0: A package for molecular simulation and trajectory analysis III. Mol Mod. 2001; 7: 306-317.
[26] Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. GROMACS: fast, flexible, and free. J Comput Chem. 2005;26(16):1701-18.
[27] Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 1997;18(15):2714-23.
[28] Dubrovsky AL, Savinskaya LA, Kornelyuk AI. Cloning and bacterial expression of the cytokine-like noncatalytic domain of bovine tyrosyl-tRNA synthetase. Biopolym Cell. 1998; 14(5):449-52.
[29] Yaremchuk A, Kriklivyi I, Tukalo M, Cusack S. Class I tyrosyl-tRNA synthetase has a class II mode of cognate tRNA recognition. EMBO J. 2002;21(14):3829-40.