Biopolym. Cell. 2007; 23(4):307-317.
http://dx.doi.org/10.7124/bc.00076E
Structure and Function of Biopolymers
Conformational mobility of human translation elongation factor A1
1, 2Kanibolotsky D. S., 1Novosil'naya A. V., 1Negrutskii B. S., 1El'skaya A. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Taras Shevchenko National University of Kyiv
    64, Volodymyrska Str., Kyiv, Ukraine, 01033

Abstract

A model of the eEF1A1 isoform of human translation elongation factor 1A has been proposed using a homology modelling method. The conformational mobility of eEF1A1 has been studied by means of multiple molecular dynamics simulation. The most essential coordinated motions in the protein have been identified using the covariance analysis of atom trajectories. It has been determined that reciprocal flexibility of domains I and II can lead to disappearance of the gap between the domains and to formation of a «closed» conformation of the protein. The amino acid residues, which are characterised by maximal flexibility of C6-atoms, have been described.
Keywords: protein synthesis, translation elongation, protein molecular dynamics
Full text: (PDF, in English) (PDF, in Russian)

References

[1] Negrutskii BS, El'skaya AV. Eukaryotic translation elongation factor 1 alpha: structure, expression, functions, and possible role in aminoacyl-tRNA channeling. Prog Nucleic Acid Res Mol Biol. 1998;60:47-78.
[2] Petrushenko ZM, Budkevich TV, Shalak VF, Negrutskii BS, El'skaya AV. Novel complexes of mammalian translation elongation factor eEF1A.GDP with uncharged tRNA and aminoacyl-tRNA synthetase. Implications for tRNA channeling. Eur J Biochem. 2002;269(19):4811-8.
[3] Thornton S, Anand N, Purcell D, Lee J. Not just for housekeeping: protein initiation and elongation factors in cell growth and tumorigenesis. J Mol Med (Berl). 2003;81(9):536-48.
[4] Ejiri S. Moonlighting functions of polypeptide elongation factor 1: from actin bundling to zinc finger protein R1-associated nuclear localization. Biosci Biotechnol Biochem. 2002;66(1):1-21.
[5] Kahns S, Lund A, Kristensen P, Knudsen CR, Clark BF, Cavallius J, Merrick WC. The elongation factor 1 A-2 isoform from rabbit: cloning of the cDNA and characterization of the protein. Nucleic Acids Res. 1998;26(8):1884-90.
[6] Anand N, Murthy S, Amann G, Wernick M, Porter LA, Cukier IH, Collins C, Gray JW, Diebold J, Demetrick DJ, Lee JM. Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer. Nat Genet. 2002;31(3):301-5.
[7] Tomlinson VA, Newbery HJ, Wray NR, Jackson J, Larionov A, Miller WR, Dixon JM, Abbott CM. Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours. BMC Cancer. 2005;5:113.
[8] Kulkarni G, Turbin DA, Amiri A, Jeganathan S, Andrade-Navarro MA, Wu TD, Huntsman DG, Lee JM. Expression of protein elongation factor eEF1A2 predicts favorable outcome in breast cancer. Breast Cancer Res Treat. 2007;102(1):31-41.
[9] Dever TE, Costello CE, Owens CL, Rosenberry TL, Merrick WC. Location of seven post-translational modifications in rabbit elongation factor 1 alpha including dimethyllysine, trimethyllysine, and glycerylphosphorylethanolamine. J Biol Chem. 1989;264(34):20518-25.
[10] Andersen GR, Pedersen L, Valente L, Chatterjee I, Kinzy TG, Kjeldgaard M, Nyborg J. Structural basis for nucleotide exchange and competition with tRNA in the yeast elongation factor complex eEF1A:eEF1Balpha. Mol Cell. 2000;6(5):1261-6.
[11] Andersen GR, Valente L, Pedersen L, Kinzy TG, Nyborg J. Crystal structures of nucleotide exchange intermediates in the eEF1A-eEF1Balpha complex. Nat Struct Biol. 2001;8(6):531-4.
[12] Vitagliano L, Masullo M, Sica F, Zagari A, Bocchini V. The crystal structure of Sulfolobus solfataricus elongation factor 1alpha in complex with GDP reveals novel features in nucleotide binding and exchange. EMBO J. 2001;20(19):5305-11.
[13] Uetsuki T, Naito A, Nagata S, Kaziro Y. Isolation and characterization of the human chromosomal gene for polypeptide chain elongation factor-1 alpha. J Biol Chem. 1989;264(10):5791-8.
[14] Norbeck J, Blomberg A. Two-dimensional electrophoretic separation of yeast proteins using a non-linear wide range (pH 3-10) immobilized pH gradient in the first dimension; reproducibility and evidence for isoelectric focusing of alkaline (pI > 7) proteins. Yeast. 1997;13(16):1519-34.
[15] She Q, Singh RK, Confalonieri F, Zivanovic Y, Allard G, Awayez MJ, Chan-Weiher CC, Clausen IG, Curtis BA, De Moors A, Erauso G, Fletcher C, Gordon PM, Heikamp-de Jong I, Jeffries AC, Kozera CJ, Medina N, Peng X, Thi-Ngoc HP, Redder P, Schenk ME, Theriault C, Tolstrup N, Charlebois RL, Doolittle WF, Duguet M, Gaasterland T, Garrett RA, Ragan MA, Sensen CW, Van der Oost J. The complete genome of the crenarchaeon Sulfolobus solfataricus P2. Proc Natl Acad Sci U S A. 2001;98(14):7835-40.
[16] Budkevich TV, Timchenko AA, Tiktopulo EI, Negrutskii BS, Shalak VF, Petrushenko ZM, Aksenov VL, Willumeit R, Kohlbrecher J, Serdyuk IN, El'skaya AV. Extended conformation of mammalian translation elongation factor 1A in solution. Biochemistry. 2002;41(51):15342-9.
[17] Schwede T, Kopp J, Guex N, Peitsch MC. SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res. 2003;31(13):3381-5.
[18] Lindahl E, Hess B, van der Spoel D. GROMACS. 3.0: a package for molecular simulation and trajectory. Analysis. J Mol Mod. 2001; 7: 306-17.
[19] Schuler LD, Daura X, van Gunsteren WF. An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase. J Comput Chem. 2001; 22(11): 1205-1218.
[20] Sch?ttelkopf AW, van Aalten DM. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D Biol Crystallogr. 2004;60(Pt 8):1355-63.
[21] H?nenberger PH, McCammon JA. Effect of artificial periodicity in simulations of biomolecules under Ewald boundary conditions: a continuum electrostatics study. Biophys Chem. 1999;78(1-2):69-88.
[22] Weber W, H?nenberger PH, McCammon JA. Molecular dynamics simulations of a polyalanine octapeptide under ewald boundary conditions: influence of artificial periodicity on peptide conformation. J Phys Chem. 2000;104(15):3668–75.
[23] Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J. Interaction models for water in relation to protein hydration. Intermolecular Forces. Ed. B. Pullman. Dordrecht: D. Reidel Publ. Company, 1981: 331-342.
[24] Hess B, Bekker H, Berendsen HJC, Fraaije JG. LINCS: A linear constraint solver for molecular simulations. J Comp Chem. 1997; 18(12): 1463-1472.
[25] Essman U, Perela L, Berkowitz ML, Darden T, Lee H, Pedersen LG. A smooth particle mesh Ewald method. J. Chem Phys. 1995; 103(19): 8577-92.
[26] Berendsen HJC, Postma JPM, DiNola A, Haak JR. Molecular dynamics with coupling to an external bath. J Chem Phys. 1984; 81(8): 3684-3690.
[27] Hess B. Convergence of sampling in protein simulations. Phys Rev E Stat Nonlin Soft Matter Phys. 2002;65(3 Pt 1):031910.
[28] Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14(1):33-8, 27-8.
[29] Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 1997;18(15):2714-23.
[30] Louise-May S, Auffinger P, Westhof E. Calculations of nucleic acid conformations. Curr Opin Struct Biol. 1996;6(3):289-98.
[31] Auffinger P, Louise-May S, Westhof E. Multiple molecular dynamics simulations of the anticodon loop of tRNAAsp in aqueous solution with counterions. J Am Chem Soc. 1995; 117(25): 6720-6.
[32] Auffinger P, Louise-May S, Westhof E. Molecular dynamics simulations of the anticodon hairpin of tRNAAsp: structuring effects of C-HO hydrogen bonds and of long-range hydration forces. J Am Chem Soc. 1996; 118(5): 1181-9.
[33] Vaiana AC, Westhof E, Auffinger P. A molecular dynamics simulation study of an aminoglycoside/A-site RNA complex: conformational and hydration patterns. Biochimie. 2006;88(8):1061-73.