Structure of the Dom34–Hbs1 complex and implications for no-go decay
- 3 October 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 17 (10), 1233-1240
- https://doi.org/10.1038/nsmb.1922
Abstract
The NoGo decay pathway involves the Dom34–Hbs1 complex and targets mRNAs that are stalled during translational elongation for cleavage. The structure of the Dom34–Hbs1 complex now reveals its structural similarity to release and elongation factor complexes. Upon binding Hbs1, Doom34 adopts a tRNA-like conformational change that suggests it would act to terminate translation. No-go decay (NGD) targets mRNAs with stalls in translation elongation for endonucleolytic cleavage in a process involving the Dom34 and Hbs1 proteins. The crystal structure of a Schizosaccharomyces pombe Dom34–Hbs1 complex reveals an overall shape similar to that of eRF1–eRF3–GTP and EF-Tu–tRNA–GDPNP. Similarly to eRF1 and GTP binding to eRF3, Dom34 and GTP bind to Hbs1 with strong cooperativity, and Dom34 acts as a GTP-dissociation inhibitor (GDI). A marked conformational change in Dom34 occurs upon binding to Hbs1, leading Dom34 to resemble a portion of a tRNA and to position a conserved basic region in a position expected to be near the peptidyl transferase center. These results support the idea that the Dom34–Hbs1 complex functions to terminate translation and thereby commit mRNAs to NGD. Consistent with this role, NGD at runs of arginine codons, which cause a strong block to elongation, is independent of the Dom34–Hbs1 complex.Keywords
This publication has 49 references indexed in Scilit:
- GTP-dependent structural rearrangement of the eRF1:eRF3 complex and eRF3 sequence motifs essential for PABP bindingNucleic Acids Research, 2009
- Analysis of Dom34 and Its Function in No-Go DecayMolecular Biology of the Cell, 2009
- A Convergence of rRNA and mRNA Quality Control Pathways Revealed by Mechanistic Analysis of Nonfunctional rRNA DecayMolecular Cell, 2009
- Structural insights into eRF3 and stop codon recognition by eRF1Genes & Development, 2009
- Nascent Peptide-dependent Translation Arrest Leads to Not4p-mediated Protein Degradation by the ProteasomeJournal of Biological Chemistry, 2009
- MolProbity: all-atom contacts and structure validation for proteins and nucleic acidsNucleic Acids Research, 2007
- Termination of translation in eukaryotes is mediated by the quaternary eRF1•eRF3•GTP•Mg2+ complex. The biological roles of eRF3 and prokaryotic RF3 are profoundly distinctNucleic Acids Research, 2006
- Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongationNature, 2006
- Coot: model-building tools for molecular graphicsActa Crystallographica Section D-Biological Crystallography, 2004
- Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamicsNature Reviews Molecular Cell Biology, 2004