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PreprintCited by 0RNA and protein synthesis mechanismsAntibiotic Resistance in BacteriaBacterial Genetics and Biotechnology

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Structural mechanism of FusB-mediated rescue from fusidic acid inhibition of protein synthesis

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González-López, Adrián, Ge, Xueliang, Larsson, Daniel S.D., Sanyal, Suparna, Selmer, Maria·2024·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2024.08.30.610483

Preprint — published as 10.1038/s41467-025-58902-3 · Paper page

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Abstract

Antibiotic resistance protein FusB rescues protein synthesis from inhibition by fusidic acid (FA), which locks elongation factor G (EF-G) to the ribosome after GTP hydrolysis. Here, we present time-resolved single-particle cryo-EM structures explaining the mechanism of FusB-mediated rescue. FusB binds to the FA-trapped EF-G on the ribosome, causing large-scale conformational changes of EF-G that break ribosome interactions. This leads to dissociation of EF-G from the ribosome, followed by FA release. We also observe two independent binding sites of FusB on the classical-state ribosome, overlapping with the binding site of EF-G to each of the ribosomal subunits, yet not inhibiting tRNA delivery. Our results reveal an intricate resistance mechanism involving specific interactions of FusB with both EF-G and the ribosome, and a non-canonical release pathway of EF-G.

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Metadata

Authors
González-López, A., Ge, X., Larsson, D. S. D., Sanyal, S., & Selmer, M.
Affiliations
Uppsala University (SE)
Corresponding author
Selmer, Maria
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2024-08-31
DOI
10.1101/2024.08.30.610483
OpenAlex
W4402112936
Cited by
0
References
1
Type
posted content
Language
en
Open access
Licence
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
fusidic acid, antibiotic resistance, elongation factor G, ribosome, protein synthesis inhibition, ribosome conformational change, ribosome binding site, time-resolved cryo-EM

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