9RTU

Structure of the 70S-EF-G(P610L)-GDP-Pi ribosome complex with tRNAs in hybrid state 1 (H1-EF-G(P610L)-GDP-Pi)

This is a non-PDB format compatible entry.

Summary for 9RTU

• Entry DOI: 10.2210/pdb9rtu/pdb
• EMDB information: 54253
• Descriptor: 50S ribosomal protein L32, 50S ribosomal protein L2, 50S ribosomal protein L3, ... (65 entities in total)
• Functional Keywords: ef-g, robosome, 70s, apramycin, translocation, ribosome, mutation
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 59
• Total formula weight: 2322005.01

Authors

Ghosh Dastidar, N.,Freyer, N.,Petrychenko, V.,Schwarzer, A.C.,Peng, B.Z.,Samatova, E.,Kothe, C.,Schmidt, M.,Peske, F.,Politi, A.,Urlaub, H.,Fischer, N.,Rodnina, M.V.,Wohlgemuth, I. (deposition date: 2025-07-03, release date: 2025-10-01, Last modification date: 2025-11-12)

Primary citation

Ghosh Dastidar, N.,Freyer, N.S.,Petrychenko, V.,de A P Schwarzer, A.C.,Peng, B.Z.,Samatova, E.,Kothe, C.,Schmidt, M.,Peske, F.,Politi, A.Z.,Urlaub, H.,Fischer, N.,Rodnina, M.V.,Wohlgemuth, I.
Selective silencing of antibiotic-tethered ribosomes as a resistance mechanism against aminoglycosides.
Nat Commun, 16:9568-9568, 2025

PubMed Abstract: Antibiotic resistance is a growing threat, underscoring the need to understand the underlying mechanisms. Aminoglycosides kill bacteria by disrupting translation fidelity, leading to the synthesis of aberrant proteins. Surprisingly, mutations in fusA, a gene encoding translation elongation factor G (EF-G), frequently confer resistance, even though EF-G neither participates in mRNA decoding nor blocks aminoglycoside binding. Here, we show that EF-G resistance variants selectively slow ribosome movement along mRNA when aminoglycosides are bound. This delay increases the chance that the drug dissociates before misreading occurs. Over several elongation cycles, this selective silencing of drug-bound ribosomes prevents error cluster formation, preserving proteome and membrane integrity. As a result, fusA mutations confer resistance early in treatment by preventing self-promoted aminoglycoside uptake. Translation on drug-free ribosomes remains sufficiently rapid to sustain near-normal bacterial growth. The mechanism of selective silencing of corrupted targets reveals a previously unrecognized antibiotic resistance strategy with potential therapeutic implications.

PubMed: 41162373
DOI: 10.1038/s41467-025-65298-7

Experimental method

ELECTRON MICROSCOPY (3 Å)