9DP7

Hypopseudouridylated yeast 80S bound with Taura syndrome virus (TSV) internal ribosome entry site (IRES) and hygromycin B, Class II

This is a non-PDB format compatible entry.

Summary for 9DP7

• Entry DOI: 10.2210/pdb9dp7/pdb
• Related: 9DOV
• EMDB information: 47098
• Descriptor: 40S ribosomal protein S0-A, 40S ribosomal protein S13, 40S ribosomal protein S14-A, ... (83 entities in total)
• Functional Keywords: rrna pseudouridylation, ires initiation, confomation, eef2, ribosome, hygromycin b
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 80
• Total formula weight: 3191544.94

Authors

Zhao, Y.,Li, H. (deposition date: 2024-09-20, release date: 2026-05-20)

Primary citation

Zhao, Y.,Xu, C.,Chen, X.,Jin, H.,Li, H.
Structural basis for hygromycin B inhibition of yeast pseudouridine-deficient ribosomes.
Sci Adv, 11:eadu0151-eadu0151, 2025

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 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.

PubMed: 40173234
DOI: 10.1126/sciadv.adu0151

Experimental method

ELECTRON MICROSCOPY (2.38 Å)