6ZVI

Mbf1-ribosome complex

Summary for 6ZVI

• Entry DOI: 10.2210/pdb6zvi/pdb
• EMDB information: 11457
• Descriptor: A/P-site tRNA, Rps5p, 40S ribosomal protein S6-A, ... (39 entities in total)
• Functional Keywords: translation, frameshifting, collision, ribosome
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 38
• Total formula weight: 1179638.31

Authors

Best, K.M.,Denk, T.,Cheng, J.,Thoms, M.,Berninghausen, O.,Beckmann, R. (deposition date: 2020-07-24, release date: 2020-09-09, Last modification date: 2024-05-01)

Primary citation

Sinha, N.K.,Ordureau, A.,Best, K.,Saba, J.A.,Zinshteyn, B.,Sundaramoorthy, E.,Fulzele, A.,Garshott, D.M.,Denk, T.,Thoms, M.,Paulo, J.A.,Harper, W.,Bennett, E.J.,Beckmann, R.,Green, R.
EDF1 coordinates cellular responses to ribosome collisions.
Elife, 9:-, 2020

PubMed Abstract: Translation of aberrant mRNAs induces ribosomal collisions, thereby triggering pathways for mRNA and nascent peptide degradation and ribosomal rescue. Here we use sucrose gradient fractionation combined with quantitative proteomics to systematically identify proteins associated with collided ribosomes. This approach identified Endothelial differentiation-related factor 1 (EDF1) as a novel protein recruited to collided ribosomes during translational distress. Cryo-electron microscopic analyses of EDF1 and its yeast homolog Mbf1 revealed a conserved 40S ribosomal subunit binding site at the mRNA entry channel near the collision interface. EDF1 recruits the translational repressors GIGYF2 and EIF4E2 to collided ribosomes to initiate a negative-feedback loop that prevents new ribosomes from translating defective mRNAs. Further, EDF1 regulates an immediate-early transcriptional response to ribosomal collisions. Our results uncover mechanisms through which EDF1 coordinates multiple responses of the ribosome-mediated quality control pathway and provide novel insights into the intersection of ribosome-mediated quality control with global transcriptional regulation.

PubMed: 32744497
DOI: 10.7554/eLife.58828

Experimental method

ELECTRON MICROSCOPY (3 Å)