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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.<\/jats:p>","DOI":"10.1093\/nar\/gkag510","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T11:33:03Z","timestamp":1778412783000},"source":"Crossref","is-referenced-by-count":2,"title":["Structural studies of nedicistrovirus IRES-driven, initiation factor-independent translation shed light on key steps of eukaryotic translation elongation"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9302-724X","authenticated-orcid":false,"given":"Swastik","family":"De","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Columbia University , New York, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara G","family":"Altomare","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University , New York, NY 10027 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina S","family":"Abaeva","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, SUNY Downstate Health Sciences University , Brooklyn, NY 11203 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prikshat","family":"Dadhwal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Columbia University , New York, NY 10032 ,","place":["United States"]},{"name":"Department of Biological Sciences, Columbia University , New York, NY 10027 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Garg","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Columbia University , New York, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Acosta-Reyes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Columbia University , New York, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuben P","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Columbia University , New York, NY 10032 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-256X","authenticated-orcid":false,"given":"Tatyana V","family":"Pestova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, SUNY Downstate Health Sciences University , Brooklyn, NY 11203 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3982-2090","authenticated-orcid":false,"given":"Christopher U T","family":"Hellen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, SUNY Downstate Health Sciences University , Brooklyn, NY 11203 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2442-1112","authenticated-orcid":false,"given":"Joachim","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Columbia University , New York, NY 10032 ,","place":["United States"]},{"name":"Department of Biological Sciences, Columbia University , New York, NY 10027 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2026060409440815800_B1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/nrm2838","article-title":"Pestova TV. 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