{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:51:25Z","timestamp":1789422685078,"version":"build-2803163510"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"14","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.science.org\/content\/page\/science-licenses-journal-article-reuse"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,4,4]]},"abstract":"<jats:p>Eukaryotic ribosomes are enriched with pseudouridine, particularly at the functional centers targeted by antibiotics. Here, we investigated the roles of pseudouridine in aminoglycoside-mediated translation inhibition by comparing the structural and functional properties of the yeast wild-type and the pseudouridine-free ribosomes. We showed that the pseudouridine-free ribosomes have decreased thermostability and high sensitivity to aminoglycosides. When presented with a model internal ribosomal entry site RNA, elongation factor eEF2, GTP (guanosine triphosphate), and sordarin, hygromycin B preferentially binds to the pseudouridine-free ribosomes during initiation by blocking eEF2 binding, stalling ribosomes in a nonrotated conformation. The structures captured hygromycin B bound at the intersubunit bridge B2a enriched with pseudouridine and a deformed codon-anticodon duplex, revealing a functional link between pseudouridine and aminoglycoside inhibition. Our results suggest that pseudouridine enhances both thermostability and conformational fitness of the ribosomes, thereby influencing their susceptibility to aminoglycosides.<\/jats:p>","DOI":"10.1126\/sciadv.adu0151","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T20:33:04Z","timestamp":1743625984000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Structural basis for hygromycin B inhibition of yeast pseudouridine-deficient ribosomes"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0485-2780","authenticated-orcid":true,"given":"Yu","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4695-6898","authenticated-orcid":true,"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, 600 S. 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