Home LiteratureArticle Details
PMID: 16675947 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structure of the unusual seryl-tRNA synthetase reveals a distinct zinc-dependent mode of substrate recognition.

The EMBO journal ·Vol. 25 ·No. 11 ·2006-06-07 ·Pages 2498-509

Bilokapic S, Maier T, Ahel D, Gruic-Sovulj I, Söll D, Weygand-Durasevic I, Ban N

Abstract

Methanogenic archaea possess unusual seryl-tRNA synthetase (SerRS), evolutionarily distinct from the SerRSs found in other archaea, eucaryotes and bacteria. The two types of SerRSs show only minimal sequence similarity, primarily within class II conserved motifs 1, 2 and 3. Here, we report a 2.5 A resolution crystal structure of the atypical methanogenic Methanosarcina barkeri SerRS and its complexes with ATP, serine and the nonhydrolysable seryl-adenylate analogue 5'-O-(N-serylsulfamoyl)adenosine. The structures reveal two idiosyncratic features of methanogenic SerRSs: a novel N-terminal tRNA-binding domain and an active site zinc ion. The tetra-coordinated Zn2+ ion is bound to three conserved protein ligands (Cys306, Glu355 and Cys461) and binds the amino group of the serine substrate. The absolute requirement of the metal ion for enzymatic activity was confirmed by mutational analysis of the direct zinc ion ligands. This zinc-dependent serine recognition mechanism differs fundamentally from the one employed by the bacterial-type SerRSs. Consequently, SerRS represents the only known aminoacyl-tRNA synthetase system that evolved two distinct mechanisms for the recognition of the same amino-acid substrate.

MeSH Terms
Adenosine Triphosphate/metabolism Amino Acid Sequence Animals Archaeal Proteins/chemistry,genetics,metabolism Binding Sites Crystallography, X-Ray Dimerization Enzyme Activation Humans Methanosarcina barkeri/enzymology Models, Molecular Molecular Sequence Data Molecular Structure Protein Structure, Quaternary Sequence Alignment Sequence Homology, Amino Acid Serine/metabolism Serine-tRNA Ligase/chemistry,genetics,metabolism Substrate Specificity Threonine/metabolism
Chemicals
Archaeal Proteins Threonine Serine Adenosine Triphosphate Serine-tRNA Ligase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bilokapic Silvija
Department of Chemistry, University of Zagreb, Zagreb, Croatia.
Maier Timm
Ahel Dragana
Gruic-Sovulj Ita
Söll Dieter
Weygand-Durasevic Ivana
Ban Nenad
References (48)
48 references, click to expand
  1. Refined crystal structure of the seryl-tRNA synthetase from Thermus thermophilus at 2.5 A resolution.
    J Mol Biol. 1993 Nov 5;234(1):222-33 PMID: 8230201
  2. The 2.9 A crystal structure of T. thermophilus seryl-tRNA synthetase complexed with tRNA(Ser).
    Science. 1994 Mar 11;263(5152):1404-10 PMID: 8128220
  3. Two classes of tRNA synthetases suggested by sterically compatible dockings on tRNA acceptor stem.
    Cell. 2001 Jan 26;104(2):191-3 PMID: 11269237
  4. Class I tyrosyl-tRNA synthetase has a class II mode of cognate tRNA recognition.
    EMBO J. 2002 Jul 15;21(14):3829-40 PMID: 12110594
  5. Sequence divergence of seryl-tRNA synthetases in archaea.
    J Bacteriol. 1998 Dec;180(24):6446-9 PMID: 9851985
  6. Dual mode recognition of two isoacceptor tRNAs by mammalian mitochondrial seryl-tRNA synthetase.
    J Biol Chem. 2001 Dec 14;276(50):46770-8 PMID: 11577083
  7. The crystal structure of the ternary complex of T.thermophilus seryl-tRNA synthetase with tRNA(Ser) and a seryl-adenylate analogue reveals a conformational switch in the active site.
    EMBO J. 1996 Jun 3;15(11):2834-42 PMID: 8654381
  8. Automated main-chain model building by template matching and iterative fragment extension.
    Acta Crystallogr D Biol Crystallogr. 2003 Jan;59(Pt 1):38-44 PMID: 12499537
  9. Shape-selective RNA recognition by cysteinyl-tRNA synthetase.
    Nat Struct Mol Biol. 2004 Nov;11(11):1134-41 PMID: 15489861
  10. Sequence, structure and evolutionary relationships between class 2 aminoacyl-tRNA synthetases: an update.
    Biochimie. 1993;75(12):1077-81 PMID: 8199242
  11. Archaeal aminoacyl-tRNA synthesis: diversity replaces dogma.
    Genetics. 1999 Aug;152(4):1269-76 PMID: 10430557
  12. tRNA recognition and evolution of determinants in seryl-tRNA synthesis.
    Nucleic Acids Res. 1999 Feb 1;27(3):721-9 PMID: 9889265
  13. tRNA-dependent aminoacyl-adenylate hydrolysis by a nonediting class I aminoacyl-tRNA synthetase.
    J Biol Chem. 2005 Jun 24;280(25):23978-86 PMID: 15845536
  14. The CCP4 suite: programs for protein crystallography.
    Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3 PMID: 15299374
  15. A succession of substrate induced conformational changes ensures the amino acid specificity of Thermus thermophilus prolyl-tRNA synthetase: comparison with histidyl-tRNA synthetase.
    J Mol Biol. 2001 Jun 15;309(4):989-1002 PMID: 11399074
  16. The unusual methanogenic seryl-tRNA synthetase recognizes tRNASer species from all three kingdoms of life.
    Eur J Biochem. 2004 Feb;271(4):694-702 PMID: 14764085
  17. Achieving error-free translation; the mechanism of proofreading of threonyl-tRNA synthetase at atomic resolution.
    Mol Cell. 2004 Nov 5;16(3):375-86 PMID: 15525511
  18. A freestanding proofreading domain is required for protein synthesis quality control in Archaea.
    Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10260-5 PMID: 15240874
  19. Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate.
    Science. 1994 Mar 11;263(5152):1432-6 PMID: 8128224
  20. Search for characteristic structural features of mammalian mitochondrial tRNAs.
    RNA. 2000 Oct;6(10):1356-79 PMID: 11073213
  21. Structural classification of HTH DNA-binding domains and protein-DNA interaction modes.
    J Mol Biol. 1996 Sep 20;262(2):294-313 PMID: 8831795
  22. Processing of X-ray diffraction data collected in oscillation mode.
    Methods Enzymol. 1997;276:307-26 PMID: 27754618
  23. Transfer ribonucleic acid-induced hydrolysis of valyladenylate bound to isoleucyl ribonucleic acid synthetase.
    J Biol Chem. 1966 Feb 25;241(4):839-45 PMID: 5324173
  24. The structural basis for seryl-adenylate and Ap4A synthesis by seryl-tRNA synthetase.
    Structure. 1995 Apr 15;3(4):341-52 PMID: 7613865
  25. Amino acid-dependent transfer RNA affinity in a class I aminoacyl-tRNA synthetase.
    J Biol Chem. 2005 Jun 24;280(25):23966-77 PMID: 15845537
  26. Seryl-tRNA synthetase from Escherichia coli: functional evidence for cross-dimer tRNA binding during aminoacylation.
    Nucleic Acids Res. 1995 Apr 11;23(7):1113-8 PMID: 7537870
  27. Dual-mode recognition of noncanonical tRNAs(Ser) by seryl-tRNA synthetase in mammalian mitochondria.
    EMBO J. 2005 Oct 5;24(19):3369-79 PMID: 16163389
  28. Probing the principles of amino acid selection using the alanyl-tRNA synthetase from Escherichia coli.
    Nucleic Acids Res. 1981 Sep 25;9(18):4627-37 PMID: 6117825
  29. Selective inhibition of divergent seryl-tRNA synthetases by serine analogues.
    FEBS Lett. 2005 Aug 15;579(20):4344-8 PMID: 16054140
  30. SHELXL: high-resolution refinement.
    Methods Enzymol. 1997;277:319-43 PMID: 18488315
  31. Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase.
    Nat Struct Biol. 2000 Jun;7(6):461-5 PMID: 10881191
  32. Improved methods for building protein models in electron density maps and the location of errors in these models.
    Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 PMID: 2025413
  33. Transfer RNA-mediated editing in threonyl-tRNA synthetase. The class II solution to the double discrimination problem.
    Cell. 2000 Dec 8;103(6):877-84 PMID: 11136973
  34. Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events.
    Genome Res. 1999 Aug;9(8):689-710 PMID: 10447505
  35. Differential modes of transfer RNASer recognition in Methanosarcina barkeri.
    J Biol Chem. 2004 Nov 19;279(47):48780-6 PMID: 15364939
  36. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs.
    Nature. 1990 Sep 13;347(6289):203-6 PMID: 2203971
  37. Aminoacyl-tRNA synthesis.
    Annu Rev Biochem. 2000;69:617-50 PMID: 10966471
  38. Glycyl-tRNA synthetase uses a negatively charged pit for specific recognition and activation of glycine.
    J Mol Biol. 1999 Mar 12;286(5):1449-59 PMID: 10064708
  39. Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process.
    Microbiol Mol Biol Rev. 2000 Mar;64(1):202-36 PMID: 10704480
  40. Evolution of different oligomeric glycyl-tRNA synthetases.
    FEBS Lett. 2005 Feb 28;579(6):1441-5 PMID: 15733854
  41. Seryl-tRNA synthetase from Escherichia coli: implication of its N-terminal domain in aminoacylation activity and specificity.
    Nucleic Acids Res. 1994 Aug 11;22(15):2963-9 PMID: 8065908
  42. Detection of noncovalent tRNA.aminoacyl-tRNA synthetase complexes by matrix-assisted laser desorption/ionization mass spectrometry.
    J Biol Chem. 1997 Dec 19;272(51):32084-91 PMID: 9405405
  43. Conformational movements and cooperativity upon amino acid, ATP and tRNA binding in threonyl-tRNA synthetase.
    J Mol Biol. 2003 Aug 1;331(1):201-11 PMID: 12875846
  44. A domain for editing by an archaebacterial tRNA synthetase.
    Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5958-63 PMID: 15079065
  45. Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases.
    Nucleic Acids Res. 1991 Jul 11;19(13):3489-98 PMID: 1852601
  46. A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A.
    Nature. 1990 Sep 20;347(6290):249-55 PMID: 2205803
  47. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
    Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 PMID: 9396791
  48. RNA-dependent cysteine biosynthesis in archaea.
    Science. 2005 Mar 25;307(5717):1969-72 PMID: 15790858
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601129
Published
2006-06-07
Epub
2006-00-04
Pages
2498-509
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1478180
Subset
IM
Databases
PDB
2CIM, 2CJ9, 2CJA, 2CJB
External Links
PubMed source DOI: 10.1038/sj.emboj.7601129 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2