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| Title | Structural basis for hygromycin B inhibition of yeast pseudouridine-deficient ribosomes. |
|---|---|
| Journal, issue, pages | Sci Adv, Vol. 11, Issue 14, Page eadu0151, Year 2025 |
| Publish date | Apr 4, 2025 |
Authors | Yu Zhao / Chong Xu / Xin Chen / Hong Jin / Hong Li / ![]() |
| PubMed Abstract | Eukaryotic ribosomes are enriched with pseudouridine, particularly at the functional centers targeted by antibiotics. Here, we investigated the roles of pseudouridine in aminoglycoside-mediated ...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. |
External links | Sci Adv / PubMed:40173234 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.38 - 2.49 Å |
| Structure data | EMDB-47093, PDB-9dov: EMDB-47098, PDB-9dp7: |
| Chemicals | ![]() ChemComp-MG: ![]() ChemComp-HYG: ![]() ChemComp-ZN: |
| Source |
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Keywords | RIBOSOME / rRNA pseudouridylation / IRES initiation / confomation / eEF2 / hygromycin B |
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