Fig. 4: PR20 and GR20 bind the polypeptide tunnels of eukaryotic 80S ribosomes.
From: Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM
a Overview of the cryo-EM structure of yeast 80S•tRNA•PR20 complex. b Cryo-EM structure of poly-PR (magenta) in the 80S tunnel (cyan); see also Supplementary Fig. 3 showing the fit of the model to the cryo-EM densities. Peptidyl-transferase center (PTC), ribosomal proteins and nucleotides, and PR repeats are labeled. c Poly-PR and interactions at the tunnel constriction at 25S rRNA nucleotide A883. Cryo-EM map (mesh) was B-factor sharpened (-32 Å2), filtered to 2.4 Å resolution, and is shown at 3 σ for PR20 and 4 σ for the ribosome. d In the rabbit 80S ribosome, PR repeats (magenta) are well resolved at the constrictions near the PTC and uL22 and are connected by lower-resolution density (modeled as gray backbone; see also Supplementary Fig. 4f–i showing the fit of the model to the cryo-EM densities). e In the rabbit 80S ribosome, GR repeats (green) bind near the PTC and stretch toward uL4 and destabilize binding of the CCA end of P-tRNA. f Steric clash between poly-PR and superimposed peptidyl-tRNA ((orange tRNA 3′ end, from PDB:5LZS), superimposed via 28S rRNA99) on the rabbit 80S ribosome suggests poly-PR competes with P-tRNA for binding to the PTC. g Poly-GR occupies the same region of the peptide tunnel as poly-PR (rabbit GR vs. yeast PR structures are shown).
