7OTC

Cryo-EM structure of an Escherichia coli 70S ribosome in complex with elongation factor G and the antibiotic Argyrin B

This is a non-PDB format compatible entry.

Summary for 7OTC

• Entry DOI: 10.2210/pdb7otc/pdb
• Related: 7UG7
• EMDB information: 13058 26486
• Descriptor: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (59 entities in total)
• Functional Keywords: antibiotic, ribosome, translation
• Biological source: Escherichia coli BL21(DE3); More
• Total number of polymer chains: 52
• Total formula weight: 2188658.26

Authors

Wieland, M.,Koller, T.O.,Wilson, D.N. (deposition date: 2021-06-10, release date: 2022-05-11, Last modification date: 2024-04-24)

Primary citation

Wieland, M.,Holm, M.,Rundlet, E.J.,Morici, M.,Koller, T.O.,Maviza, T.P.,Pogorevc, D.,Osterman, I.A.,Muller, R.,Blanchard, S.C.,Wilson, D.N.
The cyclic octapeptide antibiotic argyrin B inhibits translation by trapping EF-G on the ribosome during translocation.
Proc.Natl.Acad.Sci.USA, 119:e2114214119-e2114214119, 2022

PubMed Abstract: Argyrins are a family of naturally produced octapeptides that display promising antimicrobial activity against Pseudomonas aeruginosa. Argyrin B (ArgB) has been shown to interact with an elongated form of the translation elongation factor G (EF-G), leading to the suggestion that argyrins inhibit protein synthesis by interfering with EF-G binding to the ribosome. Here, using a combination of cryo-electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET), we demonstrate that rather than interfering with ribosome binding, ArgB rapidly and specifically binds EF-G on the ribosome to inhibit intermediate steps of the translocation mechanism. Our data support that ArgB inhibits conformational changes within EF-G after GTP hydrolysis required for translocation and factor dissociation, analogous to the mechanism of fusidic acid, a chemically distinct antibiotic that binds a different region of EF-G. These findings shed light on the mechanism of action of the argyrin-class antibiotics on protein synthesis as well as the nature and importance of rate-limiting, intramolecular conformational events within the EF-G-bound ribosome during late-steps of translocation.

PubMed: 35500116
DOI: 10.1073/pnas.2114214119

Experimental method

ELECTRON MICROSCOPY (2.9 Å)