Fig. 4: PTC rearrangements in the PF846-stalled termination complex.
From: Selective inhibition of human translation termination by a drug-like compound
a Overview of the mRNA decoding center and PTC with eRF1 (slate blue), P-site tRNA (orange), mRNA (magenta), 28S rRNA (light cyan), nascent chain (purple), and PF846 (cyan). Essential eRF1 motifs are highlighted in boxes with letters corresponding to the panel labels. b Comparison of the PTC from a bacterial RF2 ribosome complex (PDB code 6c5l11, pale green) and in the PF846-stalled termination complex. c eRF1-mediated stacking interactions within the PTC, showing eRF1 residue F190, 28S rRNA nucleotide A4518, and C74 of P-site tRNA. Spheres represent van der Waals radii of C, N, and O atoms. d Interaction network of U + 1 in the UAA stop codon (magenta) with the eRF1 NIKS motif (slate blue). Interactions proposed to stabilize the stop codon are indicated with dashed lines for hydrogen bonds and spheres for van der Waals radii. 4R-hydroxylysine (LYY63) at residue 63 in eRF1 is shown. e Comparison of the position of 28S rRNA nucleotide U4501 with Ec 23S rRNA nucleotide U2585 in the RF2-bound bacterial ribosome. The steric clash with the PF846-stalled NC is highlighted with a red “X”. f Comparison of the positions of A3887 and A4419 with the respective nucleotides in the RF2-bound bacterial ribosome (Ec A2062 and U2503), showing dashed lines for hydrogen bonds.
