Class II Aminoacyl Transfer Rna Synthetases: Crystal Structure of Yeast Aspartyl-trna Synthetase Complexed with tRNA Asp
10.1126/science.2047877
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

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 β sheet, and flanked by three α 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.

Bibliography

Ruff, M., Krishnaswamy, S., Boeglin, M., Poterszman, A., Mitschler, A., Podjarny, A., Rees, B., Thierry, J. C., & Moras, D. (1991). Class II Aminoacyl Transfer Rna Synthetases: Crystal Structure of Yeast Aspartyl-trna Synthetase Complexed with tRNA Asp. Science, 252(5013), 1682–1689.

Authors 9
  1. M. Ruff (first)
  2. S. Krishnaswamy (additional)
  3. M. Boeglin (additional)
  4. A. Poterszman (additional)
  5. A. Mitschler (additional)
  6. A. Podjarny (additional)
  7. B. Rees (additional)
  8. J. C. Thierry (additional)
  9. D. Moras (additional)
References 48 Referenced 458
  1. AMIRI, I, THE COMPLETE AMINO-ACID SEQUENCE OF CYTOPLASMIC ASPARTYL-TRANSFER RNA-SYNTHETASE FROM SACCHAROMYCES-CEREVISIAE, BIOCHIMIE 67: 607 (1985). (10.1016/S0300-9084(85)80200-5) / BIOCHIMIE (1985)
  2. ANSELME, J, ASPARAGINYL-TRANSFER-RNA SYNTHETASE FROM ESCHERICHIA-COLI HAS SIGNIFICANT SEQUENCE HOMOLOGIES WITH YEAST ASPARTYL-TRANSFER RNA-SYNTHETASE, GENE 84: 481 (1989). (10.1016/0378-1119(89)90524-6) / GENE (1989)
  3. BRICK, P, STRUCTURE OF TYROSYL TRANSFER-RNA SYNTHETASE REFINED AT 2.3-A RESOLUTION - INTERACTION OF THE ENZYME WITH THE TYROSYL ADENYLATE INTERMEDIATE, JOURNAL OF MOLECULAR BIOLOGY 208: 83 (1989). (10.1016/0022-2836(89)90090-9) / JOURNAL OF MOLECULAR BIOLOGY (1989)
  4. BRICOGNE, G, METHODS AND PROGRAMS FOR DIRECT-SPACE EXPLOITATION OF GEOMETRIC REDUNDANCIES, ACTA CRYSTALLOGRAPHICA SECTION A 32: 832 (1976). / ACTA CRYSTALLOGRAPHICA SECTION A (1976)
  5. BRUNIE, S, CRYSTALLOGRAPHIC STUDY AT 2.5A RESOLUTION OF THE INTERACTION OF METHIONYL-TRANSFER-RNA SYNTHETASE FROM ESCHERICHIA-COLI WITH ATP, JOURNAL OF MOLECULAR BIOLOGY 216: 411 (1990). (10.1016/S0022-2836(05)80331-6) / JOURNAL OF MOLECULAR BIOLOGY (1990)
  6. CUSACK, S, A 2ND CLASS OF SYNTHETASE STRUCTURE REVEALED BY X-RAY-ANALYSIS OF ESCHERICHIA-COLI SERYL-TRANSFER RNA-SYNTHETASE AT 2.5-A, NATURE 347: 249 (1990). (10.1038/347249a0) / NATURE (1990)
  7. DIETRICH, A, CRYSTALLOGRAPHIC STUDIES ON THE ASPARTYL-TRANSFER RNA SYNTHETASE-TRANSFER RNAASP SYSTEM FROM YEAST - THE CRYSTALLINE AMINOACYL TRANSFER RNA-SYNTHETASE, JOURNAL OF MOLECULAR BIOLOGY 138: 129 (1980). (10.1016/S0022-2836(80)80008-8) / JOURNAL OF MOLECULAR BIOLOGY (1980)
  8. DOCK, A.C., CRYSTALLIZATION OF TRANSFER RIBONUCLEIC-ACIDS, BIOCHIMIE 66: 179 (1984). (10.1016/0300-9084(84)90063-4) / BIOCHIMIE (1984)
  9. DOCKBREGEON, A.C., THE CONTACTS OF YEAST TRANSFER RNASER WITH SERYL-TRANSFER RNA-SYNTHETASE STUDIED BY FOOTPRINTING EXPERIMENTS, EUROPEAN JOURNAL OF BIOCHEMISTRY 188: 283 (1990). (10.1111/j.1432-1033.1990.tb15401.x) / EUROPEAN JOURNAL OF BIOCHEMISTRY (1990)
  10. Eriani, G., Nucleic Acids Research 19: 265 (1991). (10.1093/nar/19.2.265) / Nucleic Acids Research (1991)
  11. ERIANI, G, PARTITION OF TRANSFER-RNA SYNTHETASES INTO 2 CLASSES BASED ON MUTUALLY EXCLUSIVE SETS OF SEQUENCE MOTIFS, NATURE 347: 203 (1990). (10.1038/347203a0) / NATURE (1990)
  12. ERIANI, G, ASPARTYL-TRANSFER RNA-SYNTHETASE FROM ESCHERICHIA-COLI - CLONING AND CHARACTERIZATION OF THE GENE, HOMOLOGIES OF ITS TRANSLATED AMINO-ACID-SEQUENCE WITH ASPARAGINYL-TRANSFER RNA AND LYSYL-TRANSFER RNA-SYNTHETASES, NUCLEIC ACIDS RESEARCH 18: 7109 (1990). (10.1093/nar/18.23.7109) / NUCLEIC ACIDS RESEARCH (1990)
  13. FRASER, T.H., AMINO-ACIDS ARE NOT ALL INITIALLY ATTACHED TO SAME POSITION ON TRANSFER-RNA MOLECULES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 72: 3044 (1975). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1975)
  14. FREIST, W, ISOLEUCYL-TRANSFER RNA-SYNTHETASE - AN ENZYME WITH SEVERAL CATALYTIC CYCLES DISPLAYING VARIATION IN SPECIFICITY AND ENERGY-CONSUMPTION, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH 27: 773 (1988). (10.1002/anie.198807731) / ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH (1988)
  15. FREIST, W, SURVEY ON SUBSTRATE-SPECIFICITY WITH REGARD TO ATP ANALOGS OF AMINOACYL-TRANSFER RNA-SYNTHETASES FROM ESCHERICHIA-COLI AND FROM BAKERS-YEAST - CORRELATION TO SYNTHETASE FAMILIES, HOPPE-SEYLERS ZEITSCHRIFT FUR PHYSIOLOGISCHE CHEMIE 362: 1247 (1981). (10.1515/bchm2.1981.362.2.1247) / HOPPE-SEYLERS ZEITSCHRIFT FUR PHYSIOLOGISCHE CHEMIE (1981)
  16. Gangloff, J., Nature New Biology 230:726 (1971). / Nature New Biology (1971)
  17. GIEGE, R, CRYSTALLIZATION OF THE COMPLEX FORMED BETWEEN YEAST TRANSFER-RNA ASP AND ITS HOMOLOGOUS AMINOACYL-TRANSFER RNA-SYNTHETASE, COMPTES RENDUS HEBDOMADAIRES DES SEANCES DE L ACADEMIE DES SCIENCES SERIE D 291: 393 (1980). / COMPTES RENDUS HEBDOMADAIRES DES SEANCES DE L ACADEMIE DES SCIENCES SERIE D (1980)
  18. HECK, J.D., VALYL-TRANSFER RNA-SYNTHETASE GENE OF ESCHERICHIA-COLI-K12 - PRIMARY STRUCTURE AND HOMOLOGY WITHIN A FAMILY OF AMINOACYL-TRANSFER RNA-SYNTHETASES, JOURNAL OF BIOLOGICAL CHEMISTRY 263: 868 (1988). (10.1016/S0021-9258(19)35434-1) / JOURNAL OF BIOLOGICAL CHEMISTRY (1988)
  19. Hou, Y.-M., Nature 333:140 (1988). (10.1038/333140a0) / Nature (1988)
  20. HOUNTONDJI, C, METHIONYL-TRANSFER RNA-SYNTHETASE FROM ESCHERICHIA-COLI - PRIMARY STRUCTURE AT THE BINDING-SITE FOR THE 3'-END OF TRANSFER-RNA F(MET), BIOCHEMISTRY 24: 1175 (1985). (10.1021/bi00326a018) / BIOCHEMISTRY (1985)
  21. HOUNTONDJI, C, SEQUENCE SIMILARITIES AMONG THE FAMILY OF AMINOACYL-TRANSFER RNA-SYNTHETASES, BIOCHIMIE 68: 1071 (1986). (10.1016/S0300-9084(86)80181-X) / BIOCHIMIE (1986)
  22. 10.1107/S0021889878013308
  23. KERN, D, PURIFICATION AND SOME PROPERTIES OF ALANYL-TRANSFER AND LEUCYL-TRANSFER RNA-SYNTHETASES FROM BAKERS-YEAST, BIOCHIMICA ET BIOPHYSICA ACTA 653: 83 (1981). (10.1016/0005-2787(81)90106-4) / BIOCHIMICA ET BIOPHYSICA ACTA (1981)
  24. KERN, D, THE 3 CYSTEINE RESIDUES OF CYTOPLASMIC ASPARTYL TRANSFER-RNA SYNTHETASE FROM SACCHAROMYCES-CEREVISIAE ARE NOT ESSENTIAL FOR ITS ACTIVITY, EUROPEAN JOURNAL OF BIOCHEMISTRY 193: 97 (1990). (10.1111/j.1432-1033.1990.tb19309.x) / EUROPEAN JOURNAL OF BIOCHEMISTRY (1990)
  25. 10.1126/science.185.4149.435
  26. LEVEQUE, F, HOMOLOGY OF LYSS AND LYSU, THE 2 ESCHERICHIA-COLI GENES ENCODING DISTINCT LYSYL TRANSFER-RNA SYNTHETASE SPECIES, NUCLEIC ACIDS RESEARCH 18: 305 (1990). (10.1093/nar/18.2.305) / NUCLEIC ACIDS RESEARCH (1990)
  27. 10.1126/science.2452483
  28. MORAS, D, CRYSTAL-STRUCTURE OF YEAST TRANSFER RNA-ASP, NATURE 288: 669 (1980). (10.1038/288669a0) / NATURE (1980)
  29. MORAS, D, ANTICODON-ANTICODON INTERACTION INDUCES CONFORMATIONAL-CHANGES IN TRANSFER-RNA - YEAST TRANSFER-RNA ASP, A MODEL FOR TRANSFER-RNA MESSENGER-RNA RECOGNITION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 932 (1986). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1986)
  30. NICHOLAS, H.B., COMPARISON OF TRANSFER-RNA SEQUENCES, COMPUTER APPLICATIONS IN THE BIOSCIENCES 3: 53 (1987). / COMPUTER APPLICATIONS IN THE BIOSCIENCES (1987)
  31. NORMANLY, J, TRANSFER-RNA IDENTITY, ANNUAL REVIEW OF BIOCHEMISTRY 58: 1029 (1989). (10.1146/annurev.bi.58.070189.005121) / ANNUAL REVIEW OF BIOCHEMISTRY (1989)
  32. PERRET, V, RELAXATION OF A TRANSFER-RNA SPECIFICITY BY REMOVAL OF MODIFIED NUCLEOTIDES, NATURE 344: 787 (1990). (10.1038/344787a0) / NATURE (1990)
  33. PODJARNY, A, YEAST TRANSFER RNAASP-ASPARTYL-TRANSFER RNA-SYNTHETASE COMPLEX - LOW RESOLUTION CRYSTAL-STRUCTURE, JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS 5: 187 (1987). (10.1080/07391102.1987.10506389) / JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS (1987)
  34. PRIESTLE, J.P., RIBBON - A STEREO CARTOON DRAWING PROGRAM FOR PROTEINS, JOURNAL OF APPLIED CRYSTALLOGRAPHY 21: 572 (1988). (10.1107/S0021889888005746) / JOURNAL OF APPLIED CRYSTALLOGRAPHY (1988)
  35. Rich, A., Horizons in Biochemistry: 103 (1962). / Horizons in Biochemistry (1962)
  36. RICH, A, STRUCTURAL ORGANIZATION OF COMPLEXES OF TRANSFERRNAS WITH AMINOACYL TRANSFER-RNA SYNTHETASES, NUCLEIC ACIDS RESEARCH 4: 1649 (1977). (10.1093/nar/4.5.1649) / NUCLEIC ACIDS RESEARCH (1977)
  37. RISLER, J.L., NATURE 292: 385 (1981). / NATURE (1981)
  38. 10.1038/250546a0
  39. ROSSMANN, M.G., CHEMICAL AND BIOLOGICAL EVOLUTION OF A NUCLEOTIDE-BINDING PROTEIN, NATURE 250: 194 (1974). (10.1038/250194a0) / NATURE (1974)
  40. 10.1126/science.2479982
  41. RUFF, M, A HIGH-RESOLUTION DIFFRACTING CRYSTAL FORM OF THE COMPLEX BETWEEN YEAST TRANSFER RNAASP AND ASPARTYL-TRANSFER RNA-SYNTHETASE, JOURNAL OF MOLECULAR BIOLOGY 201: 235 (1988). (10.1016/0022-2836(88)90450-0) / JOURNAL OF MOLECULAR BIOLOGY (1988)
  42. RUFF M unpublished data.
  43. SELLAMI, M, NUCLEOTIDE-SEQUENCE OF THE GENE CODING FOR YEAST CYTOPLASMIC ASPARTYL-TRANSFER RNA-SYNTHETASE (APS) - MAPPING OF THE 5' AND 3' TERMINI OF ASPRS MESSENGER-RNA, NUCLEIC ACIDS RESEARCH 14: 1657 (1986). (10.1093/nar/14.4.1657) / NUCLEIC ACIDS RESEARCH (1986)
  44. SHARP, K.A., ELECTRICAL POTENTIAL OF TRANSFER-RNAS - CODON ANTICODON RECOGNITION, BIOCHEMISTRY 29: 340 (1990). (10.1021/bi00454a006) / BIOCHEMISTRY (1990)
  45. VON DER HAAR, F, BIOCHEMISTRY-US 15: 4131 (1976). (10.1021/bi00663a034) / BIOCHEMISTRY-US (1976)
  46. WANG, B.C., RESOLUTION OF PHASE AMBIGUITY IN MACROMOLECULAR CRYSTALLOGRAPHY, METHODS IN ENZYMOLOGY 115: 90 (1985). (10.1016/0076-6879(85)15009-3) / METHODS IN ENZYMOLOGY (1985)
  47. 10.1126/science.6390679
  48. WESTHOF, E, CRYSTALLOGRAPHIC REFINEMENT OF YEAST ASPARTIC-ACID TRANSFER-RNA, JOURNAL OF MOLECULAR BIOLOGY 184: 119 (1985). (10.1016/0022-2836(85)90048-8) / JOURNAL OF MOLECULAR BIOLOGY (1985)
Dates
Type When
Created 18 years, 10 months ago (Oct. 5, 2006, 6:10 p.m.)
Deposited 1 year, 7 months ago (Jan. 11, 2024, 10:20 p.m.)
Indexed 2 months ago (June 27, 2025, 4:03 p.m.)
Issued 34 years, 2 months ago (June 21, 1991)
Published 34 years, 2 months ago (June 21, 1991)
Published Print 34 years, 2 months ago (June 21, 1991)
Funders 0

None

@article{Ruff_1991, title={Class II Aminoacyl Transfer Rna Synthetases: Crystal Structure of Yeast Aspartyl-trna Synthetase Complexed with tRNA Asp}, volume={252}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.2047877}, DOI={10.1126/science.2047877}, number={5013}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Ruff, M. and Krishnaswamy, S. and Boeglin, M. and Poterszman, A. and Mitschler, A. and Podjarny, A. and Rees, B. and Thierry, J. C. and Moras, D.}, year={1991}, month=jun, pages={1682–1689} }