Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 21 June 1991:
Vol. 252. no. 5013, pp. 1682 - 1689
DOI: 10.1126/science.2047877
Prev | Table of Contents | Next

Articles

Science, Vol 252, Issue 5013, 1682-1689
Copyright © 1991 by American Association for the Advancement of Science

articles

Class II aminoacyl transfer RNA synthetases: crystal structure of yeast aspartyl-tRNA synthetase complexed with tRNA(Asp)

M Ruff, S Krishnaswamy, M Boeglin, A Poterszman, A Mitschler, A Podjarny, B Rees, JC Thierry, and D Moras

Laboratoire de Cristallographie Biologique, Institut de Biologie Moleculaire et Cellulaire du CNRS, Universite Louis Pasteur, Strasbourg, France.

The crystal structure of the binary complex tRNA(Asp)-aspartyl tRNA synthetase from yeast was solved with the use of multiple isomorphous replacement to 3 angstrom resolution. The dimeric synthetase, a member of class II aminoacyl tRNA synthetases (aaRS's) exhibits the characteristic signature motifs conserved in eight aaRS's. These three sequence motifs are contained in the catalytic site domain, built around an antiparallel beta sheet, and flanked by three alpha helices that form the pocket in which adenosine triphosphate (ATP) and the CCA end of tRNA bind. The tRNA(Asp) molecule approaches the synthetase from the variable loop side. The two major contact areas are with the acceptor end and the anticodon stem and loop. In both sites the protein interacts with the tRNA from the major groove side. The correlation between aaRS class II and the initial site of aminoacylation at 3'-OH can be explained by the structure. The molecular association leads to the following features: (i) the backbone of the GCCA single-stranded portion of the acceptor end exhibits a regular helical conformation; (ii) the loop between residues 320 and 342 in motif 2 interacts with the acceptor stem in the major groove and is in contact with the discriminator base G and the first base pair UA; and (iii) the anticodon loop undergoes a large conformational change in order to bind the protein. The conformation of the tRNA molecule in the complex is dictated more by the interaction with the protein than by its own sequence.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Plasmodial Aspartyl-tRNA Synthetases and Peculiarities in Plasmodium falciparum.
T. Bour, A. Akaddar, B. Lorber, S. Blais, C. Balg, E. Candolfi, and M. Frugier (2009)
J. Biol. Chem. 284, 18893-18903
   Abstract »    Full Text »    PDF »
Pyrrolo-C as a molecular probe for monitoring conformations of the tRNA 3' end.
C.-M. Zhang, C. Liu, T. Christian, H. Gamper, J. Rozenski, D. Pan, J. B. Randolph, E. Wickstrom, B. S. Cooperman, and Y.-M. Hou (2008)
RNA 14, 2245-2253
   Abstract »    Full Text »    PDF »
Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation.
M. Guo, M. Ignatov, K. Musier-Forsyth, P. Schimmel, and X.-L. Yang (2008)
PNAS 105, 2331-2336
   Abstract »    Full Text »    PDF »
Ammonium Scanning in an Enzyme Active Site: THE CHIRAL SPECIFICITY OF ASPARTYL-tRNA SYNTHETASE.
D. Thompson, C. Lazennec, P. Plateau, and T. Simonson (2007)
J. Biol. Chem. 282, 30856-30868
   Abstract »    Full Text »    PDF »
In silico detection of tRNA sequence features characteristic to aminoacyl-tRNA synthetase class membership.
E. Jako, P. Ittzes, A. Szenes, A. Kun, E. Szathmary, and G. Pal (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Molecular Dynamics Simulations Show That Bound Mg2+ Contributes to Amino Acid and Aminoacyl Adenylate Binding Specificity in Aspartyl-tRNA Synthetase through Long Range Electrostatic Interactions.
D. Thompson and T. Simonson (2006)
J. Biol. Chem. 281, 23792-23803
   Abstract »    Full Text »    PDF »
Structure of human tryptophanyl-tRNA synthetase in complex with tRNATrp reveals the molecular basis of tRNA recognition and specificity.
N. Shen, L. Guo, B. Yang, Y. Jin, and J. Ding (2006)
Nucleic Acids Res. 34, 3246-3258
   Abstract »    Full Text »    PDF »
Compilation of mRNA Polyadenylation Signals in Arabidopsis Revealed a New Signal Element and Potential Secondary Structures.
J. C. Loke, E. A. Stahlberg, D. G. Strenski, B. J. Haas, P. C. Wood, and Q. Q. Li (2005)
Plant Physiology 138, 1457-1468
   Abstract »    Full Text »    PDF »
Initiation of Protein Synthesis in Bacteria.
B. S. Laursen, H. P. Sorensen, K. K. Mortensen, and H. U. Sperling-Petersen (2005)
Microbiol. Mol. Biol. Rev. 69, 101-123
   Abstract »    Full Text »    PDF »
An RNA Ligase from Deinococcus radiodurans.
A. Martins and S. Shuman (2004)
J. Biol. Chem. 279, 50654-50661
   Abstract »    Full Text »    PDF »
A yeast arginine specific tRNA is a remnant aspartate acceptor.
A. Fender, R. Geslain, G. Eriani, R. Giege, M. Sissler, and C. Florentz (2004)
Nucleic Acids Res. 32, 5076-5086
   Abstract »    Full Text »    PDF »
Aminoacylation properties of pathology-related human mitochondrial tRNALys variants.
M. SISSLER, M. HELM, M. FRUGIER, R. GIEGE, and C. FLORENTZ (2004)
RNA 10, 841-853
   Abstract »    Full Text »    PDF »
A new {gamma}-interferon-inducible promoter and splice variants of an anti-angiogenic human tRNA synthetase.
J. Liu, E. Shue, K. L. Ewalt, and P. Schimmel (2004)
Nucleic Acids Res. 32, 719-727
   Abstract »    Full Text »    PDF »
The Conserved Cys-X1-X2-Cys Motif Present in the TtcA Protein Is Required for the Thiolation of Cytidine in Position 32 of tRNA from Salmonella enterica serovar Typhimurium.
G. Jager, R. Leipuviene, M. G. Pollard, Q. Qian, and G. R. Bjork (2004)
J. Bacteriol. 186, 750-757
   Abstract »    Full Text »    PDF »
Genetic, Enzymatic, and Structural Analyses of Phenylalanyl-tRNA Synthetase from Thermococcus kodakaraensis KOD1.
K. Shiraki, M. Tsuji, Y. Hashimoto, K. Fujimoto, S. Fujiwara, M. Takagi, and T. Imanaka (2003)
J. Biochem. 134, 567-574
   Abstract »    Full Text »    PDF »
Anticodon Recognition in Evolution: SWITCHING tRNA SPECIFICITY OF AN AMINOACYL-tRNA SYNTHETASE BY SITE-DIRECTED PEPTIDE TRANSPLANTATION.
A. Brevet, J. Chen, S. Commans, C. Lazennec, S. Blanquet, and P. Plateau (2003)
J. Biol. Chem. 278, 30927-30935
   Abstract »    Full Text »    PDF »
Yeast tRNAAsp Charging Accuracy Is Threatened by the N-terminal Extension of Aspartyl-tRNA Synthetase.
M. Ryckelynck, R. Giege, and M. Frugier (2003)
J. Biol. Chem. 278, 9683-9690
   Abstract »    Full Text »    PDF »
Functional Dissection of the Eukaryotic-specific tRNA-interacting Factor of Lysyl-tRNA Synthetase.
M. Francin and M. Mirande (2003)
J. Biol. Chem. 278, 1472-1479
   Abstract »    Full Text »    PDF »
Crystal Structure of Hyperthermophilic Archaeal Initiation Factor 5A: A Homologue of Eukaryotic Initiation Factor 5A (eIF-5A).
M. Yao, A. Ohsawa, S. Kikukawa, I. Tanaka, and M. Kimura (2003)
J. Biochem. 133, 75-81
   Abstract »    Full Text »    PDF »
BRCA2 Function in DNA Binding and Recombination from a BRCA2-DSS1-ssDNA Structure.
H. Yang, P. D. Jeffrey, J. Miller, E. Kinnucan, Y. Sun, N. H. Thoma, N. Zheng, P.-L. Chen, W.-H. Lee, and N. P. Pavletich (2002)
Science 297, 1837-1848
   Abstract »    Full Text »    PDF »
Transition State Stabilization by the N-terminal Anticodon-binding Domain of Lysyl-tRNA Synthetase.
T. Takita and K. Inouye (2002)
J. Biol. Chem. 277, 29275-29282
   Abstract »    Full Text »    PDF »
Conformational change of Escherichia coli initiator methionyl-tRNAfMet upon binding to methionyl-tRNA formyl transferase.
C. Mayer and U. L. RajBhandary (2002)
Nucleic Acids Res. 30, 2844-2850
   Abstract »    Full Text »    PDF »
NMR Analysis of Bovine tRNATrp. CONFORMATION DEPENDENCE OF Mg2+ BINDING.
Q. Gong, Q. Guo, K.-L. Tong, G. Zhu, J. T.-F. Wong, and H. Xue (2002)
J. Biol. Chem. 277, 20694-20701
   Abstract »    Full Text »    PDF »
Crystal Structure of the N-terminal Segment of Human Eukaryotic Translation Initiation Factor 2alpha.
M. C. Nonato, J. Widom, and J. Clardy (2002)
J. Biol. Chem. 277, 17057-17061
   Abstract »    Full Text »    PDF »
Modulation of tRNAAla identity by inorganic pyrophosphatase.
A. D. Wolfson and O. C. Uhlenbeck (2002)
PNAS 99, 5965-5970
   Abstract »    Full Text »    PDF »
Formation of Two Classes of tRNA Synthetases in Relation to Editing Functions and Genetic Code.
P. SCHIMMEL and L. RIBAS DE POUPLANA (2001)
Cold Spring Harb Symp Quant Biol 66, 161-166
   Abstract »    PDF »
tRNA Conformity.
A.D. WOLFSON, F.J. LARIVIERE, J.A. PLEISS, T. DALE, H. ASAHARA, and O.C. UHLENBECK (2001)
Cold Spring Harb Symp Quant Biol 66, 185-194
   Abstract »    PDF »
Importance of discriminator base stacking interactions: molecular dynamics analysis of A73 microhelixAla variants.
M. C. Nagan, P. Beuning, K. Musier-Forsyth, and C. J. Cramer (2000)
Nucleic Acids Res. 28, 2527-2534
   Abstract »    Full Text »    PDF »
NMR Studies of Bacillus subtilis tRNATrp Hyperexpressed in Escherichia coli. ASSIGNMENT OF IMINO PROTON SIGNALS AND DETERMINATION OF THERMAL STABILITY.
X. Yan, H. Xue, H. Liu, J. Hang, J. T.-F. Wong, and G. Zhu (2000)
J. Biol. Chem. 275, 6712-6716
   Abstract »    Full Text »    PDF »
Identification of Discriminator Base Atomic Groups That Modulate the Alanine Aminoacylation Reaction.
A. E. Fischer, P. J. Beuning, and K. Musier-Forsyth (1999)
J. Biol. Chem. 274, 37093-37096
   Abstract »    Full Text »    PDF »
Domain-domain communication in a miniature archaebacterial tRNA synthetase.
B. A. Steer and P. Schimmel (1999)
PNAS 96, 13644-13649
   Abstract »    Full Text »    PDF »
Aminoacyl tRNA synthetases as targets for new anti-infectives.
P. Schimmel, J. Tao, and J. Hill (1998)
FASEB J 12, 1599-1609
   Abstract »    Full Text »
Activation of microhelix charging by localized helix destabilization.
R. W. Alexander, B. E. Nordin, and P. Schimmel (1998)
PNAS 95, 12214-12219
   Abstract »    Full Text »    PDF »
cpc-3, the Neurospora crassa Homologue of Yeast GCN2, Encodes a Polypeptide with Juxtaposed eIF2alpha Kinase and Histidyl-tRNA Synthetase-related Domains Required for General Amino Acid Control.
E. Sattlegger, A. G. Hinnebusch, and I. B. Barthelmess (1998)
J. Biol. Chem. 273, 20404-20416
   Abstract »    Full Text »    PDF »
Evolution of a Transfer RNA Gene Through a Point Mutation in the Anticodon.
M. E. Saks, J. R. Sampson, and J. Abelson (1998)
Science 279, 1665-1670
   Abstract »    Full Text »
The importance of tRNA backbone-mediated interactions with synthetase for aminoacylation.
W. H. McClain, J. Schneider, S. Bhattacharya, and K. Gabriel (1998)
PNAS 95, 460-465
   Abstract »    Full Text »    PDF »
Engineering a tRNA and aminoacyl-tRNA synthetase for the site-specific incorporation of unnatural amino acids into proteins in vivo.
D. R. Liu, T. J. Magliery, M. Pastrnak, and P. G. Schultz (1997)
PNAS 94, 10092-10097
   Abstract »    Full Text »    PDF »
Human Lysyl-tRNA Synthetase Accepts Nucleotide 73 Variants and Rescues Escherichia coli Double-defective Mutant.
K. Shiba, T. Stello, H. Motegi, T. Noda, K. Musier-Forsyth, and P. Schimmel (1997)
J. Biol. Chem. 272, 22809-22816
   Abstract »    Full Text »    PDF »
Translational Regulation of Yeast GCN4. A WINDOW ON FACTORS THAT CONTROL INITIATOR-tRNA BINDING TO THE RIBOSOME.
A. G. Hinnebusch (1997)
J. Biol. Chem. 272, 21661-21664
   Full Text »    PDF »
Crystal structure of the homo-tetrameric DNA binding domain of Escherichia coli single-stranded DNA-binding protein determined by multiwavelength x-ray diffraction on the selenomethionyl protein at 2.9-A resolution.
S. Raghunathan, C. S. Ricard, T. M. Lohman, and G. Waksman (1997)
PNAS 94, 6652-6657
   Abstract »    Full Text »    PDF »
A 2'-Phosphotransferase Implicated in tRNA Splicing Is Essential in Saccharomyces cerevisiae.
G. M. Culver, S. M. McCraith, S. A. Consaul, D. R. Stanford, and E. M. Phizicky (1997)
J. Biol. Chem. 272, 13203-13210
   Abstract »    Full Text »    PDF »
Defining the Active Site of Yeast Seryl-tRNA Synthetase. MUTATIONS IN MOTIF 2LOOP RESIDUES AFFECT tRNA-DEPENDENT AMINO ACID RECOGNITION.
B. Lenhard, B. Lenhard, I. Landeka, and D. Soll (1997)
J. Biol. Chem. 272, 1136-1141
   Abstract »    Full Text »    PDF »
Widespread Use of the Glu-tRNAGln Transamidation Pathway among Bacteria. A MEMBER OF THE alpha PURPLE BACTERIA LACKS GLUTAMINYL-tRNA SYNTHETASE.
Y. Gagnon, L. Lacoste, N. Champagne, and J. Lapointe (1996)
J. Biol. Chem. 271, 14856-14863
   Abstract »    Full Text »    PDF »
Visualizing a Specific Contact in the HIV-1 Tat Protein Fragment and trans-Activation Responsive Region RNA Complex by Photocross-linking.
Y. Liu, Z. Wang, and T. M. Rana (1996)
J. Biol. Chem. 271, 10391-10396
   Abstract »    Full Text »    PDF »
Solution Structure of a Bovine Immunodeficiency Virus Tat-TAR Peptide-RNA Complex.
J. D. Puglisi, L. Chen, S. Blanchard, and A. D. Frankel (1995)
Science 270, 1200-1203
   Abstract »    PDF »
Architectures of class-defining and specific domains of glutamyl-tRNA synthetase.
O Nureki, D. Vassylyev, K Katayanagi, T Shimizu, S Sekine, T Kigawa, T Miyazawa, S Yokoyama, and K Morikawa (1995)
Science 267, 1958-1965
   Abstract »    PDF »
Mutational isolation of a sieve for editing in a transfer RNA synthetase.
E Schmidt and P Schimmel (1994)
Science 264, 265-267
   Abstract »    PDF »
The 2.9 A crystal structure of T. thermophilus seryl-tRNA synthetase complexed with tRNA(Ser).
V Biou, A Yaremchuk, M Tukalo, and S Cusack (1994)
Science 263, 1404-1410
   Abstract »    PDF »
The transfer RNA identity problem: a search for rules.
M. Saks, Sampson JR, and J. Abelson (1994)
Science 263, 191-197
   Abstract »    PDF »
Major groove accessibility of RNA.
K. Weeks and D. Crothers (1993)
Science 261, 1574-1577
   Abstract »    PDF »
Conformation of the TAR RNA-arginine complex by NMR spectroscopy.
J. Puglisi, R Tan, B. Calnan, A. Frankel, and Williamson JR (1992)
Science 257, 76-80
   Abstract »    PDF »
Overlapping nucleotide determinants for specific aminoacylation of RNA microhelices.
C Francklyn, J. Shi, and P Schimmel (1992)
Science 255, 1121-1125
   Abstract »    PDF »
Identity elements for specific aminoacylation of yeast tRNA(Asp) by cognate aspartyl-tRNA synthetase.
J Putz, J. Puglisi, C Florentz, and R Giege (1991)
Science 252, 1696-1699
   Abstract »    PDF »
A Novel Anti-tumor Cytokine Contains an RNA Binding Motif Present in Aminoacyl-tRNA Synthetases.
Y. Kim, J. Shin, R. Li, C. Cheong, K. Kim, and S. Kim (2000)
J. Biol. Chem. 275, 27062-27068
   Abstract »    Full Text »    PDF »
Magnesium Ion-mediated Binding to tRNA by an Amino-terminal Peptide of a Class II tRNA Synthetase.
R. Hammamieh and D. C. H. Yang (2001)
J. Biol. Chem. 276, 428-433
   Abstract »    Full Text »    PDF »
Importance of the Anticodon Sequence in the Aminoacylation of tRNAs by Methionyl-tRNA Synthetase and by Valyl-tRNA Synthetase in an Archaebacterium.
V. Ramesh and U. L. RajBhandary (2001)
J. Biol. Chem. 276, 3660-3665
   Abstract »    Full Text »    PDF »
Divergent Adaptation of tRNA Recognition by Methanococcus jannaschii Prolyl-tRNA Synthetase.
B. Burke, R. S. A. Lipman, K. Shiba, K. Musier-Forsyth, and Y.-M. Hou (2001)
J. Biol. Chem. 276, 20286-20291
   Abstract »    Full Text »    PDF »
Operational RNA Code for Amino Acids in Relation to Genetic Code in Evolution.
L. Ribas de Pouplana and P. Schimmel (2001)
J. Biol. Chem. 276, 6881-6884
   Full Text »    PDF »
From the Cover: Structural and mutational studies of the recognition of the arginine tRNA-specific major identity element, A20, by arginyl-tRNA synthetase.
A. Shimada, O. Nureki, M. Goto, S. Takahashi, and S. Yokoyama (2001)
PNAS 98, 13537-13542
   Abstract »    Full Text »    PDF »
Novel Protein Domains and Repeats in Drosophila melanogaster: Insights into Structure, Function, and Evolution.
C. P. Ponting, R. Mott, P. Bork, and R. R. Copley (2001)
Genome Res. 11, 1996-2008
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)