Evidence map›Paper›PMID 35500116›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

The cyclic octapeptide antibiotic argyrin B inhibits translation by trapping EF-G on the ribosome during translocation.

Maximiliane Wieland, Mikael Holm, Emily J Rundlet, Martino Morici, Timm O Koller, Tinashe P Maviza, Domen Pogorevc, Ilya A Osterman, Rolf Müller, Scott C Blanchard and 1 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
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  6. The Structural and Molecular Mechanisms ofMolecules (Basel, Switzerland) · 2024
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Maximiliane WielandInstitute for Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany.ORCID 0000-0002-6261-0117
Mikael HolmSt. Jude Children's Research Hospital, Memphis, TN 38105.
Emily J RundletSt. Jude Children's Research Hospital, Memphis, TN 38105.ORCID 0000-0003-4041-6206
Martino MoriciInstitute for Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany.ORCID 0000-0002-7304-5264
Timm O KollerInstitute for Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany.ORCID 0000-0003-0145-4891
Tinashe P MavizaCenter of Life Sciences, Skolkovo Institute of Science and Technology, 121205 Moscow, Russia.ORCID 0000-0001-8676-7445
Domen PogorevcDepartment Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research, Saarland University, 66123 Saarbrücken,Germany.
Ilya A OstermanCenter of Life Sciences, Skolkovo Institute of Science and Technology, 121205 Moscow, Russia.ORCID 0000-0001-7748-980X
Rolf MüllerDepartment Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research, Saarland University, 66123 Saarbrücken,Germany.
Scott C BlanchardSt. Jude Children's Research Hospital, Memphis, TN 38105.ORCID 0000-0003-2717-9365
Daniel N WilsonInstitute for Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany.ORCID 0000-0003-3816-3828
Universität Hamburg · DESt. Jude Children's Research Hospital · USHelmholtz Centre for Infection Research · DESkolkovo Institute of Science and Technology · RU

Funding

Imaging Protein Synthesis on the Ribosome using Single-Molecule FRETR01GM079238 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BLANCHARD, SCOTT C · 2006 to 2023
$7.0M
Tri-Institutional PhD Program in Chemical BiologyT32GM115327 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI TAN, DEREK S · 2015 to 2019
$741k
NIGMS NIH HHS R01 GM079238NIGMS NIH HHS T32 GM115327
6 · The paper itself

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.

Indexed as

Anti-Bacterial AgentsPeptide Elongation Factor GFusidic AcidHumansOligopeptidesRibosomesTranslocation, GeneticAnti-Bacterial Agentsargyrin BFusidic AcidOligopeptidesPeptide Elongation Factor Gantibioticargyrinfusidic acidribosometranslocation

Identifiers

PMID35500116
PMCPMC9171646
OpenAlexW4225291600

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.