title: Structure of the no-go mRNA decay complex Dom34-Hbs1 bound to a stalled 80S ribosome.
abstract: No-go decay (NGD) is a mRNA quality-control mechanism in eukaryotic cells that leads to degradation of mRNAs stalled during translational elongation. The key factors triggering NGD are Dom34 and Hbs1. We used cryo-EM to visualize NGD intermediates resulting from binding of the Dom34-Hbs1 complex to stalled ribosomes. At subnanometer resolution, all domains of Dom34 and Hbs1 were identified, allowing the docking of crystal structures and homology models. Moreover, the close structural similarity of Dom34 and Hbs1 to eukaryotic release factors (eRFs) enabled us to propose a model for the ribosome-bound eRF1-eRF3 complex. Collectively, our data provide structural insights into how stalled mRNA is recognized on the ribosome and how the eRF complex can simultaneously recognize stop codons and catalyze peptide release.
authors.affiliation: Gene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany. becker@lmb.uni-muenchen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Armache
authors.forename: Alexander
authors.initials: A
authors.lastname: Jarasch
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Anger
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Villa
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Sieber
authors.forename: Basma Abdel
authors.initials: BA
authors.lastname: Motaal
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mielke
authors.forename: Otto
authors.initials: O
authors.lastname: Berninghausen
authors.forename: Roland
authors.initials: R
authors.lastname: Beckmann
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D008958:Models, Molecular; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D018797:Cell Cycle Proteins; C077247:HBS1 protein, S cerevisiae; D018840:HSP70 Heat-Shock Proteins; D010445:Peptide Elongation Factors; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C112808:Dom34 protein, S cerevisiae; D004722:Endoribonucleases; D019204:GTP-Binding Proteins