Biopolym. Cell. 2007; 23(5):449-460.
http://dx.doi.org/10.7124/bc.000780
Bioinformatics
Bioinformatical analysis of influence of human tyrosyl-tRNA synthetase mutations associated with neuropathy Charcot-Marie-Tooth, type C, on its local spatial structure properties
1Odynets K. A., 1Kornelyuk A. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

A causal relationship between three independent mutant forms of the human cytoplasmic tyrosyl-tRNA synthetase (TyrRS) and dominant Charcot-Marie-Tooth neuropathy, type C, (DI-CMTC) has been recently reported . In this article we carried out the bioinformatical investigation of the effect of amino acid residues change in the cases of two point mutations Gly41Arg, Glu196Lys and deletion 153–156delVKQV on structural properties of catalytic module dimer of TyrRS (2 × 39 kDa or, so called, mini-TyrRS), especially on its local environment and electrostatic potential of molecular surface of the protein.
Keywords: tyrosyl-tRNA synthetase, neuropathy Charcot-Marie-Tooth type C, spatial structure, computer mutagenesis
Full text: (PDF, in English) (PDF, in Ukrainian)

References

[1] Park SG, Ewalt KL, Kim S. Functional expansion of aminoacyl-tRNA synthetases and their interacting factors: new perspectives on housekeepers. Trends Biochem Sci. 2005;30(10):569-74.
[2] Ivakhno SS, Kornelyuk AI. Cytokine-like activities of some aminoacyl-tRNA synthetases and auxiliary p43 cofactor of aminoacylation reaction and their role in oncogenesis. Exp Oncol. 2004;26(4):250-5. .
[3] Antonellis A, Lee-Lin SQ, Wasterlain A, Leo P, Quezado M, Goldfarb LG, Myung K, Burgess S, Fischbeck KH, Green ED. Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons. J Neurosci. 2006;26(41):10397-406.
[4] Nangle LA, Zhang W, Xie W, Yang XL, Schimmel P. Charcot-Marie-Tooth disease-associated mutant tRNA synthetases linked to altered dimer interface and neurite distribution defect. Proc Natl Acad Sci U S A. 2007;104(27):11239-44.
[5] Jordanova A, Irobi J, Thomas FP, Van Dijck P, Meerschaert K, Dewil M, Dierick I, Jacobs A, De Vriendt E, Guergueltcheva V, Rao CV, Tournev I, Gondim FA, D'Hooghe M, Van Gerwen V, Callaerts P, Van Den Bosch L, Timmermans JP, Robberecht W, Gettemans J, Thevelein JM, De Jonghe P, Kremensky I, Timmerman V. Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy. Nat Genet. 2006;38(2):197-202.
[6] Jordanova A, Thomas FP, Guergueltcheva V, Tournev I, Gondim FA, Ishpekova B, De Vriendt E, Jacobs A, Litvinenko I, Ivanova N, Buzhov B, De Jonghe P, Kremensky I, Timmerman V. Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35. Am J Hum Genet. 2003;73(6):1423-30.
[7] Kornelyuk AI. Structural and functional investigation of mammalian tyrosyl-tRNA synthetase. Biopolym Cell. 1998;14(4):349-59.
[8] 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.
[9] Lee JW, Beebe K, Nangle LA, Jang J, Longo-Guess CM, Cook SA, Davisson MT, Sundberg JP, Schimmel P, Ackerman SL. Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration. Nature. 2006;443(7107):50-5.
[10] Roy H, Ibba M. Molecular biology: sticky end in protein synthesis. Nature. 2006;443(7107):41-2.
[11] Paley EL, Denisova G, Sokolova O, Posternak N, Wang X, Brownell AL. Tryptamine induces tryptophanyl-tRNA synthetase-mediated neurodegeneration with neurofibrillary tangles in human cell and mouse models. Neuromolecular Med. 2007;9(1):55-82.
[12] Paley EL, Smelyanski L, Malinovskii V, Subbarayan PR, Berdichevsky Y, Posternak N, Gershoni JM, Sokolova O, Denisova G. Mapping and molecular characterization of novel monoclonal antibodies to conformational epitopes on NH2 and COOH termini of mammalian tryptophanyl-tRNA synthetase reveal link of t
[13] Berger P, Niemann A, Suter U. Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease). Glia. 2006;54(4):243-57.
[14] Meyer zu H?rste G, Prukop T, Nave KA, Sereda MW. Myelin disorders: Causes and perspectives of Charcot-Marie-Tooth neuropathy. J Mol Neurosci. 2006;28(1):77-88.
[15] Vallat JM, Tazir M, Magdelaine C, Sturtz F, Grid D. Autosomal-recessive Charcot-Marie-Tooth diseases. J Neuropathol Exp Neurol. 2005;64(5):363-70.
[16] Shy ME. Charcot-Marie-Tooth disease: an update. Curr Opin Neurol. 2004;17(5):579-85.
[17] Roa BB, Greenberg F, Gunaratne P, Sauer CM, Lubinsky MS, Kozma C, Meck JM, Magenis RE, Shaffer LG, Lupski JR. Duplication of the PMP22 gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1 neuropathy. Hum Genet. 1996;97(5):642-9.
[18] Bruzzone R, White TW, Scherer SS, Fischbeck KH, Paul DL. Null mutations of connexin32 in patients with X-linked Charcot-Marie-Tooth disease. Neuron. 1994;13(5):1253-60.
[19] Ionasescu VV. Charcot-Marie-Tooth neuropathies: from clinical description to molecular genetics. Muscle Nerve. 1995;18(3):267-75.
[20] Guilbot A, Williams A, Ravis? N, Verny C, Brice A, Sherman DL, Brophy PJ, LeGuern E, Delague V, Bareil C, M?garban? A, Claustres M. A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease. Hum Mol Genet. 2001;10(4):415-21.
[21] Bolino A, Muglia M, Conforti FL, LeGuern E, Salih MA, Georgiou DM, Christodoulou K, Hausmanowa-Petrusewicz I, Mandich P, Schenone A, Gambardella A, Bono F, Quattrone A, Devoto M, Monaco AP. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet. 2000;25(1):17-9.
[22] 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.
[23] Wakasugi K, Slike BM, Hood J, Ewalt KL, Cheresh DA, Schimmel P. Induction of angiogenesis by a fragment of human tyrosyl-tRNA synthetase. J Biol Chem. 2002;277(23):20124-6.
[24] Jia J, Li B, Jin Y, Wang D. Expression, purification, and characterization of human tyrosyl-tRNA synthetase. Protein Expr Purif. 2003;27(1):104-8.
[25] 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.
[26] Wakasugi K, Schimmel P. Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science. 1999;284(5411):147-51.
[27] Ewalt KL, Schimmel P. Activation of angiogenic signaling pathways by two human tRNA synthetases. Biochemistry. 2002;41(45):13344-9.
[28] Tzima E, Schimmel P. Inhibition of tumor angiogenesis by a natural fragment of a tRNA synthetase. Trends Biochem Sci. 2006;31(1):7-10.
[29] Yang XL, Skene RJ, McRee DE, Schimmel P. Crystal structure of a human aminoacyl-tRNA synthetase cytokine. Proc Natl Acad Sci U S A. 2002;99(24):15369-74.
[30] Yang XL, Otero FJ, Skene RJ, McRee DE, Schimmel P, Ribas de Pouplana L. Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains. Proc Natl Acad Sci U S A. 2003;100(26):15376-80.
[31] Kobayashi T, Nureki O, Ishitani R, Yaremchuk A, Tukalo M, Cusack S, Sakamoto K, Yokoyama S. Structural basis for orthogonal tRNA specificities of tyrosyl-tRNA synthetases for genetic code expansion. Nat Struct Biol. 2003;10(6):425-32.
[32] Tsunoda M, Kusakabe Y, Tanaka N, Ohno S, Nakamura M, Senda T, Moriguchi T, Asai N, Sekine M, Yokogawa T, Nishikawa K, Nakamura KT. Structural basis for recognition of cognate tRNA by tyrosyl-tRNA synthetase from three kingdoms. Nucleic Acids Res. 2007;35(13):4289-300.
[33] Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235-42.
[34] Laskowski RA, Chistyakov VV, Thornton JM. PDBsum more: new summaries and analyses of the known 3D structures of proteins and nucleic acids. Nucleic Acids Res. 2005;33(Database issue):D266-8.
[35] Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 1997;18(15):2714-23.
[36] Fiser A, Sali A. ModLoop: automated modeling of loops in protein structures. Bioinformatics. 2003;19(18):2500-1.
[37] Schwede T, Kopp J, Guex N, Peitsch MC. SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res. 2003;31(13):3381-5.
[38] Mart?-Renom MA, Stuart AC, Fiser A, S?nchez R, Melo F, Sali A. Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct. 2000;29:291-325.
[39] Fraczkiewicz R, Braun W. Exact and efficient analytical calculation of the accessible surface areas and their gradients for macromolecules. J. Comp. Chem. 1998. 19: 319-333.
[40] Landau M, Mayrose I, Rosenberg Y, Glaser F, Martz E, Pupko T, Ben-Tal N. ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information. Nucl. Acids Res. 2005. 33, Web Server issue: W299-W302.
[41] Wakasugi K, Quinn CL, Tao N, Schimmel P. Genetic code in evolution: switching species-specific aminoacylation with a peptide transplant. EMBO J. 1998;17(1):297-305.