PXD062129

PXD062129 is an original dataset announced via ProteomeXchange.

Title	Structural mechanism of FusB-mediated rescue from fusidic acid inhibition of protein synthesis
Description	The 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 interactions with the ribosome, tRNA, and mRNA. 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. The affinity of FusB to the ribosome and the concentration of FusB in S. aureus during FusB-mediated resistance support that direct binding of FusB to ribosomes could occur in the cell. 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_07:28:50.908.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Fuchs
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-21 10:47:43	ID requested
⏵ 1	2025-05-07 07:28:51	announced

10.1038/s41467-025-58902-3;

Gonz, á, lez-L, ó, pez A, Ge X, Larsson DSD, Sihlbom Wallem C, Sanyal S, Selmer M, Structural mechanism of FusB-mediated rescue from fusidic acid inhibition of protein synthesis. Nat Commun, 16(1):3693(2025) [pubmed]

submitter keyword: cryo-EM, elongation factor G, ribosome,Fusidic acid, FusB

Carina Sihlbom Wallem
contact affiliation	Proteomics Core Facility, University of Gothenburg
contact email	carina.sihlbom@gu.se
lab head
Johannes Fuchs
contact affiliation	Gothenburg University
contact email	johannes.fuchs@gu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062129
     1. Label: PRIDE project
     2. Name: Structural mechanism of FusB-mediated rescue from fusidic acid inhibition of protein synthesis