Home LiteratureArticle Details
PMID: 18988853 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Insights into translational termination from the structure of RF2 bound to the ribosome.

Science (New York, N.Y.) ·Vol. 322 ·No. 5903 ·2008-11-07 ·Pages 953-6

Weixlbaumer A, Jin H, Neubauer C, Voorhees RM, Petry S, Kelley AC, Ramakrishnan V

Abstract

The termination of protein synthesis occurs through the specific recognition of a stop codon in the A site of the ribosome by a release factor (RF), which then catalyzes the hydrolysis of the nascent protein chain from the P-site transfer RNA. Here we present, at a resolution of 3.5 angstroms, the crystal structure of RF2 in complex with its cognate UGA stop codon in the 70S ribosome. The structure provides insight into how RF2 specifically recognizes the stop codon; it also suggests a model for the role of a universally conserved GGQ motif in the catalysis of peptide release.

MeSH Terms
Amino Acid Motifs Bacterial Proteins/chemistry,metabolism Biocatalysis Codon, Terminator/chemistry,metabolism Crystallography, X-Ray Hydrogen Bonding Models, Molecular Peptide Chain Termination, Translational Peptide Termination Factors/chemistry,metabolism Peptides/metabolism Protein Conformation Protein Structure, Secondary Protein Structure, Tertiary RNA, Bacterial/metabolism RNA, Transfer/metabolism Ribosome Subunits/chemistry,metabolism Ribosomes/chemistry,metabolism Thermus thermophilus/chemistry
Chemicals
Bacterial Proteins Codon, Terminator Peptide Termination Factors Peptides RNA, Bacterial peptide chain termination release factor 2 RNA, Transfer
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Weixlbaumer Albert
Medical Research Council (MRC) Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Jin Hong
Neubauer Cajetan
Voorhees Rebecca M
Petry Sabine
Kelley Ann C
Ramakrishnan Venki
References (31)
31 references, click to expand
  1. A post-translational modification in the GGQ motif of RF2 from Escherichia coli stimulates termination of translation.
    EMBO J. 2000 Dec 15;19(24):6900-7 PMID: 11118225
  2. Functional sites of interaction between release factor RF1 and the ribosome.
    Nat Struct Biol. 2000 Oct;7(10):866-70 PMID: 11017194
  3. Recognition of cognate transfer RNA by the 30S ribosomal subunit.
    Science. 2001 May 4;292(5518):897-902 PMID: 11340196
  4. Bacterial polypeptide release factor RF2 is structurally distinct from eukaryotic eRF1.
    Mol Cell. 2001 Dec;8(6):1375-82 PMID: 11779511
  5. Release of peptide promoted by the GGQ motif of class 1 release factors regulates the GTPase activity of RF3.
    Mol Cell. 2002 Oct;10(4):789-98 PMID: 12419223
  6. Selection of tRNA by the ribosome requires a transition from an open to a closed form.
    Cell. 2002 Nov 27;111(5):721-32 PMID: 12464183
  7. The essential role of the invariant GGQ motif in the function and stability in vivo of bacterial release factors RF1 and RF2.
    Mol Microbiol. 2003 Jan;47(1):267-75 PMID: 12492870
  8. A cryo-electron microscopic study of ribosome-bound termination factor RF2.
    Nature. 2003 Jan 2;421(6918):87-90 PMID: 12511960
  9. Structure of the Escherichia coli ribosomal termination complex with release factor 2.
    Nature. 2003 Jan 2;421(6918):90-4 PMID: 12511961
  10. The active site of the ribosome is composed of two layers of conserved nucleotides with distinct roles in peptide bond formation and peptide release.
    Cell. 2004 May 28;117(5):589-99 PMID: 15163407
  11. Polypeptide chain termination in vitro: isolation of a release factor.
    Proc Natl Acad Sci U S A. 1967 Sep;58(3):1144-51 PMID: 5233840
  12. Single amino acid substitution in prokaryote polypeptide release factor 2 permits it to terminate translation at all three stop codons.
    Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8165-9 PMID: 9653158
  13. Mutations in the highly conserved GGQ motif of class 1 polypeptide release factors abolish ability of human eRF1 to trigger peptidyl-tRNA hydrolysis.
    RNA. 1999 Aug;5(8):1014-20 PMID: 10445876
  14. Structural insights into translational fidelity.
    Annu Rev Biochem. 2005;74:129-77 PMID: 15952884
  15. An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA.
    Nature. 2005 Nov 24;438(7067):520-4 PMID: 16306996
  16. The SAXS solution structure of RF1 differs from its crystal structure and is similar to its ribosome bound cryo-EM structure.
    Mol Cell. 2005 Dec 22;20(6):929-38 PMID: 16364917
  17. Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon.
    Cell. 2005 Dec 29;123(7):1255-66 PMID: 16377566
  18. Deletion of a conserved, central ribosomal intersubunit RNA bridge.
    Mol Cell. 2006 Sep 15;23(6):865-74 PMID: 16973438
  19. Structure of the 70S ribosome complexed with mRNA and tRNA.
    Science. 2006 Sep 29;313(5795):1935-42 PMID: 16959973
  20. Release factors 2 from Escherichia coli and Thermus thermophilus: structural, spectroscopic and microcalorimetric studies.
    Nucleic Acids Res. 2007;35(4):1343-53 PMID: 17272297
  21. An intact ribose moiety at A2602 of 23S rRNA is key to trigger peptidyl-tRNA hydrolysis during translation termination.
    Nucleic Acids Res. 2007;35(15):5130-40 PMID: 17660192
  22. A model for how ribosomal release factors induce peptidyl-tRNA cleavage in termination of protein synthesis.
    Mol Cell. 2007 Sep 7;27(5):758-66 PMID: 17803940
  23. Two distinct components of release factor function uncovered by nucleophile partitioning analysis.
    Mol Cell. 2007 Nov 9;28(3):458-67 PMID: 17996709
  24. Stop codon recognition by release factors induces structural rearrangement of the ribosomal decoding center that is productive for peptide release.
    Mol Cell. 2007 Nov 30;28(4):533-43 PMID: 18042450
  25. Pseudouridylation of helix 69 of 23S rRNA is necessary for an effective translation termination.
    Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19410-5 PMID: 18032607
  26. Peptide release on the ribosome depends critically on the 2' OH of the peptidyl-tRNA substrate.
    RNA. 2008 Aug;14(8):1526-31 PMID: 18567817
  27. Structural basis for translation termination on the 70S ribosome.
    Nature. 2008 Aug 14;454(7206):852-7 PMID: 18596689
  28. Peptide release on the ribosome: mechanism and implications for translational control.
    Annu Rev Microbiol. 2008;62:353-73 PMID: 18544041
  29. The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis.
    Cell. 2000 Feb 4;100(3):311-21 PMID: 10676813
  30. A tripeptide 'anticodon' deciphers stop codons in messenger RNA.
    Nature. 2000 Feb 10;403(6770):680-4 PMID: 10688208
  31. The accuracy of codon recognition by polypeptide release factors.
    Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2046-51 PMID: 10681447
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1164840
Published
2008-11-07
Pages
953-6
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2642913
Subset
IM
Grants
Wellcome Trust · 082086 · United Kingdom
Medical Research Council · MC_U105184332 · United Kingdom
Medical Research Council · U.1051.04.018(78935) · United Kingdom
Databases
PDB
2JL5, 2JL6, 2JL7, 2JL8
Corrections
CommentIn
PMID: 18988828
External Links
PubMed source DOI: 10.1126/science.1164840 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