9Q2T

NediV IRES in complex with Rabbit 80S ribosome with eEF2 and P site Ala-tRNA

This is a non-PDB format compatible entry.

Summary for 9Q2T

• Entry DOI: 10.2210/pdb9q2t/pdb
• EMDB information: 72175
• Descriptor: 40S ribosomal protein S3, 40S ribosomal protein S20, 40S ribosomal protein S25, ... (86 entities in total)
• Functional Keywords: ribosome, ires, translation, initiation
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 84
• Total formula weight: 3309740.32

Authors

De, S.,Altomare, C.G.,Abaeva, I.S.,Dadhwal, P.,Garg, P.,Acosta-Reyes, F.,Brown, Z.P.,Pestova, T.V.,Hellen, C.U.T.,Frank, J. (deposition date: 2025-08-15, release date: 2026-06-17)

Primary citation

De, S.,Altomare, C.G.,Abaeva, I.S.,Dadhwal, P.,Garg, P.,Acosta-Reyes, F.,Brown, Z.P.,Pestova, T.V.,Hellen, C.U.T.,Frank, J.
Structural studies of nedicistrovirus IRES-driven, initiation factor-independent translation shed light on key steps of eukaryotic translation elongation.
Nucleic Acids Res., 54:-, 2026

PubMed Abstract: We utilized the nedicistrovirus (NediV) intergenic region (IGR) internal ribosomal entry site (IRES)-mediated, initiation factor-independent translation initiation system and determined high-resolution structures of 80S ribosome complexes with the NediV IRES in various functional states, including binary complexes, aminoacyl-transfer RNA (tRNA)-bound complexes, and complexes with elongation factor eEF2. In binary complexes, the NediV IRES primarily occupies the ribosomal P site, exhibiting conformational flexibility and engaging the ribosome at multiple interaction sites. Upon translocation, the IRES undergoes structural rearrangements, including destabilization of its PKI domain, facilitating the transition to canonical elongation. Crucially, we captured an eEF2-bound complex, along with an eEF1A-bound failed decoding complex featuring a mismatched tRNA, the latter representing the first instance of a canonical elongation complex visualized in the presence of a natural, hydrolysable nucleotide and without the addition of any trapping agents. These findings provide a comprehensive structural overview of IGR IRES-mediated translation initiation and its transition to elongation, revealing key mechanistic details of viral translation and proofreading.

PubMed: 42240621
DOI: 10.1093/nar/gkag510

Experimental method

ELECTRON MICROSCOPY (4.1 Å)