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7UG7

70S ribosome complex in an intermediate state of translocation bound to EF-G(GDP) stalled by Argyrin B

This is a non-PDB format compatible entry.
Summary for 7UG7
Entry DOI10.2210/pdb7ug7/pdb
Related7OTC
EMDB information13058 26486
Descriptor16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (67 entities in total)
Functional Keywordstranslocation, ef-g, argyrin, ribosome
Biological sourceEscherichia coli K-12
More
Total number of polymer chains60
Total formula weight2354273.41
Authors
Rundlet, E.J.,Wieland, M.,Holm, M.,Koller, T.O.,Blanchard, S.C.,Wilson, D.N. (deposition date: 2022-03-24, release date: 2022-05-18, Last modification date: 2025-03-19)
Primary citationWieland, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.58 Å)
Structure validation

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