Biopolym. Cell. 2012; 28(5):397-403.
Flexible 3D structure of Bos taurus tyrosyl-tRNA synthetase suggests the existence of hinge mechanism provided by conservative Gly353 at interdomain linker
1Pydiura N. A., 1Kornelyuk A. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


Mammalian tyrosyl-tRNA synthetase is composed of two structural modules: N-terminal catalytic miniTyrRS and non-catalytic cytokine-like C-terminal module connected by a flexible peptide linker. Till now, the 3D structure of any full-length mammalian TyrRS has not been solved by X-ray crystallography. The aim of this work was a homology modeling of 3D structure of full-lehgth B. taurus tyrosyl-tRNA synthetase. Methods. Homology modeling of TyrRS was performed by Modeller 9.1 package. Quality of the models was assessed using Biotech Validation Suite web-server. Results. Our BLAST search identified 34 % sequence homology between interdomain linker of TyrRS and linker of human c-Abl tyrosine kinase. In order to model the full-length TyrRS structure we assembled the models of three parts of the protein (N- and C- terminal domains and the linker) using Modeller 9.1 software. The best Abl-17 model structure was refined by energy minimization. Conclusions. High flexibility of the interdomain linker can generate multiple conformations of TyrRS. The hinge mechanism at interdomain linker may be provided by conservative Gly353. It is proposed, that due to the linker flexibility an open extended conformation of TyrRS could transform into closed conformations in the enzyme-substrate complexes.
Keywords: tyrosyl-tRNA synthetase, homology modeling, interdomain linker, c-Abl tyrosine kinase, EMAP II, tRNATyr


[1] Kornelyuk A. I. Structural and functional investigation of mammalian tyrosyl-tRNA synthetase Biopolym. Cell 1998 14, N 4:349–359.
[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 O. V., Naidenov V. G., Odynets K. A., Woodmaska M. I., Matsuka G. Kh., Kornelyuk A. I. Homology of C-terminal noncatalytic domain of mammalian tyrosyl-tRNA synthetase with cytokine EMAP II and non-catalytic domains of methionyland phenylalanyl-tRNA synthetases Biopolym. Cell 1997 13, N 6:474–478.
[4] Kleeman T. A., Wei D., Simpson K. L., First E. A. Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine J. Biol. Chem 1997 272, N 22:14420– 14425.
[5] Kao J., Ryan J., Brett G., Chen J., Shen H., Fan Y. G., Godman G., Familletti P. C., Wang F., Pan Y. C., Stern D., Clauss M. Endothelial monocyte-activating polypeptide II. A novel tumor-derived polypeptide that activates host-response mechanisms J. Biol. Chem 1992 267, N 28:20239–20247.
[6] Kao J., Houck K., Fan Y., Haehnel I., Libutti S. K., Kayton M. L., Grikscheit T., Chabot J., Nowygrod R., Greenberg S., Kuang W.-J., Leung D., Hayward J. R., Kisiel W., Heath M., Brett J., Stern D. M. Characterization of a novel tumor-derived cytokine. Endothelial monocyte-activating polypeptide II J. Biol. Chem 1994 269, N 40:25106–25119.
[7] Tas M. P., Murray J. C. Endothelial monocyte-activating polypeptide II Int. J. Biochem. Cell. Biol 1996 28, N 8:837– 841.
[8] Ivakhno S. S., Kornelyuk O. I. Cytokine activities of some aminoacyl-tRNA synthetases and auxiliary cofactors of aminoacylation reaction Exp. Oncol 2004 26, N 4:250–255.
[9] Levanets O. V., Naidenov V. G., Woodmaska M. I., Matsuka G. H., Kornelyuk A. I. Cloning of cDNA encoding C-terminal part of mammalian tyrosyl-tRNA synthetase using of PCR-amplified radioactive probe Biopolym. Cell 1997 13, N 2:121–126.
[10] Simos G., Sauer A., Fasiolo F., Hurt E. C. A conserved domain within Arc1p delivers tRNA to aminoacyl-tRNA synthetases Mol. Cell 1998 1, N 2:235–242.
[11] Tan M., Heckmann K., Brunen-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, N 1–2:131–140.
[12] Simos G., Segref A., Fasiolo F., Hellmuth K., Shevchenko A., Mann M., Hurt E. C. The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyland glutamyl-tRNA synthetases EMBO J 1996 15, N 19:5437–5448.
[13] Kurochkin I. V., Kornelyuk A. I., Matsuka G. Kh. Interaction of eukaryotic tyrosyl-tRNA synthetases with high molecular weight RNA Mol. Biol. (Moscow) 1991 25, N 3:779–786.
[14] Peng K., Radivojac P., Vucetic S., Dunker A. K., Obradovic Z. Length-dependent prediction of protein intrinsic disorder BMC Bioinformatics 2006 7:208.
[15] Dosztanyi Z., Csizmok V., Tompa P., Simon I. Web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content Bioinformatics 2005 21, N 16:3433–3434.
[16] Berman H. M., Westbrook J., Feng Z., Gilliland G., Bhat T. N., Weissig H., Shindyalov I. N., Bourne P. E. The protein data bank Nucleic Acids Res 2000 28, N 1:235–242.
[17] Guex N., Peitsch M. C. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling Electrophoresis 1997 18, N 15:2714–2723.
[18] DeLano W. L. The PyMOL Molecular Graphics System San Carlos: DeLano Scientific, 2002.
[19] Persistence of Vision Pty. Ltd, Persistence of Vision Raytracer (Version 3.6) 2004.
[20] Baker N. A., Sept D., Joseph S., Holst M. J., McCammon J. A. Electrostatics of nanosystems: application to microtubules and the ribosome Proc. Natl Acad. Sci. USA 2001 98, N 18:10037–10041.
[21] Holst M., Saied F. Numerical solution of the nonlinear PoissonBoltzmann equation: Developing more robust and efficient methods J. Comput. Chem 1995 16, N 3:337–364.
[22] Elofsson A., Fischer D., Rice D. W., Le Grand S. M., Eisenberg D. A study of combined structure/sequence profiles Fold Des 1996 1, N 6:451–461.
[23] Larkin M. A., Blackshields G., Brown N. P., Chenna R., McGettigan P. A., McWilliam H., Valentin F., Wallace I. M., Wilm A., Lopez R., Thompson J. D., Gibson T. J., Higgins, D. G. Clustal W and Clustal X version 2 Bioinformatics 2007 23, N 21:2947–2948.
[24] Goujon M., McWilliam H., Li W., Valentin F., Squizzato S., Paern J., Lopez R. A new bioinformatics analysis tools framework at EMBL-EBI Nucleic Acids Res 2010 38 (Web Server issue) W695–699.
[25] Fiser A., Sali A. Modeller: generation and refinement of homology-based protein structure models Methods Enzymol 2003 374:461–491.
[26] Laskowski R. A., MacArthur M. W., Moss D. S., Thornton J. M. PROCHECK: a program to check the stereochemical quality of protein structures J. Appl. Cryst 1993 26, N 2:283–291.
[27] Yang X. L., Skene R. J., McRee D. E., Schimmel P. Crystal structure of a human aminoacyl-tRNA synthetase cytokine Proc. Natl Acad. Sci. USA 2002 99, N 24:15369–15374.
[28] Yang X. L., Liu J., Skene R. J., McRee D. E., Schimmel P. Crystal structure of an EMAP-II-like cytokine released from a human tRNA synthetase Helv. Chim. Acta 2003 86, N 4:1246– 1257.
[29] Minasov G., Shuvalova L., Brunzelle J. S., Collart F. R., Anderson W. F., Mcsg. Crystal structure of an uncharacterized B. cereus protein PDB: 1X7F.
[30] Nagar B., Hantschel O., Young M. A., Scheffzek K., Veach D., Bornmann W., Clarkson B., Superti-Furga G., Kuriyan J. Structural basis for the autoinhibition of c-Abl tyrosine kinase Cell 2003 112, N 6:859–871 .
[31] Odynets K. A., Kornelyuk A. I. Analysis of unstructured regions of human cytoplasmic tyrosyl-tRNAsynthetase by methods of bioinformatics Biopolym. Cell 2005 21, N 5:445–452.
[32] Olszak K., Solecka K., Odynets K. A., Przykorska A., Kornelyuk A. I. The analysis of the complex between cytokine-like COOHterminal module of mammalian tyrosyl-tRNA synthetase and tRNA Abstrs of the 29th Meet. of FEBS Warsaw, 2004:54.
[33] Wong L., Lieser S., Chie-Leon B., Miyashita O., Aubol B., Shaffer J., Onuchic J. N., Jennings P. A., Woods V. L. Jr., Adams J. A. Dynamic coupling between the SH2 domain and active site of the COOH terminal Src kinase, Csk J. Mol. Biol 2004 341, N 1:93–106.
[34] Pydiura N. A., Tereshchenko F. A., Kornelyuk A. I. Conformational flexibility of interdomain linker in bovine tyrosyl-tRNA synthetase studied by molecular dynamics simulation Biopolym. Cell 2006 22, N 6:433–438.
[35] Wriggers W., Chakravarty S., Jennings P. A. Control of protein functional dynamics by peptide linkers Biopolymers 2005 80, N 6:736–746.