FIG. 6.
Model of translation termination inhibition by uORF2. The ribosome translates through uORF2 until the uORF2 peptide attached to the cognate tRNAPro for the terminal proline codon (CCU) is positioned in the ribosomal P site, while the stop codon (UAA) is in the A site. At this point eRF1 enters the ribosomal A site, recognizes the stop codon, and binds to the ribosome. During the termination reaction, the glycines of the eRF1 GGQ motif and the two terminal prolines of uORF2 (black circles) interact, possibly through the peptidyl-transferase center (PTC, indicated by the shaded oval), to form an intermediate that stabilizes the peptidyl-tRNA bond. This stabilization contributes to prolonged ribosomal stalling, which in turn blocks ribosomes from scanning to the downstream UL4 cistron. Residues of the uORF2 peptidyl-tRNA that are needed for inhibition of downstream translation but that do not interact with eRF1 (shaded circles) may interact with other ribosomal proteins or associated factors.