9RHU

Rabbit 80S ribosome in complex with eRF1-AAQ, stalled at the Stop codon in mutated F2A sequence

This is a non-PDB format compatible entry.

Summary for 9RHU

• Entry DOI: 10.2210/pdb9rhu/pdb
• EMDB information: 53976
• Descriptor: 60S ribosomal protein L34, 5.8S rRNA, Ubiquitin-ribosomal protein eS31 fusion protein, ... (94 entities in total)
• Functional Keywords: translation, recoding, nascent peptide, foot-and-mouth disease virus, f2a, stopgo, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 88
• Total formula weight: 4184111.65

Authors

Li, X.,Zuber, P.K.,Loughran, G.,Bhatt, P.R.,Alquraish, F.,Ramakrishnan, V.,Firth, A.E.,Atkins, J.F. (deposition date: 2025-06-10, release date: 2026-01-21, Last modification date: 2026-02-18)

Primary citation

Li, X.,Zuber, P.K.,Loughran, G.,Bhatt, P.R.,Alquraish, F.,Ramakrishnan, V.,Firth, A.E.,Atkins, J.F.
Molecular architecture and diversity of StopGo/2A translational recoding.
Proc.Natl.Acad.Sci.USA, 123:e2528667123-e2528667123, 2026

PubMed Abstract: Viral 2A sequences trigger a cotranslational 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 multigene expression in biotechnology.

PubMed: 41576085
DOI: 10.1073/pnas.2528667123

Experimental method

ELECTRON MICROSCOPY (2.65 Å)