The study determined the cryo-EM structure of the mammalian ribosome at the F2A site, revealing a mechanism for StopGo translational recoding in viruses.
Structural and bioinformatic characterization of the StopGo/2A mechanism reveals how nascent peptide interactions remodel the ribosomal catalytic center and expands the known diversity of functional recoding motifs.
Absolute Event Rate: 0% vs 0%
Viral 2A sequences trigger a co-translational peptide bond formation “skipping” event, termed “StopGo”, to generate two separate proteins from a single open reading frame without classical termination. To investigate the mechanism of StopGo, we determined the cryo-EM structure of a mammalian ribosome positioned at the foot-and-mouth disease virus 2A (F2A) site. The structure shows how interactions between the F2A nascent chain (NC) and the ribosomal exit tunnel induce a conformational change in the peptidyl transferase center that precludes further translation elongation but instead pre-exposes the P-tRNA:F2A-NC ester bond for hydrolysis and NC release. Additionally, we bioinformatically characterized variation and host association across nearly 10,000 StopGo sequences identified in virus genomes. We expanded the canonical core motif to (D/G/C/N)(V/I)ExNPGP and identified additional rare but functional variants. We also revealed several distinct upstream motifs that we showed biochemically to be important for StopGo activity. Interestingly, although StopGo is known to be functionally active in plants, we found no evidence for natural utilization of StopGo by plant viruses. Overall, these findings provide valuable insights into a unique translation recoding mechanism, and lay foundations for further optimization of multi-gene expression in biotechnology.
Firth et al. (Tue,) reported a other. The study determined the cryo-EM structure of the mammalian ribosome at the F2A site, revealing a mechanism for StopGo translational recoding in viruses.