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TitleRegulation of the macrolide resistance ABC-F translation factor MsrD.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 3891, Year 2023
Publish dateJul 1, 2023
AuthorsCorentin R Fostier / Farès Ousalem / Elodie C Leroy / Saravuth Ngo / Heddy Soufari / C Axel Innis / Yaser Hashem / Grégory Boël /
PubMed AbstractAntibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are proliferating among pathogens. Here, we ...Antibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are proliferating among pathogens. Here, we combine genetic and structural approaches to determine the regulation of streptococcal ARE ABC-F gene msrD in response to macrolide exposure. We show that binding of cladinose-containing macrolides to the ribosome prompts insertion of the leader peptide MsrDL into a crevice of the ribosomal exit tunnel, which is conserved throughout bacteria and eukaryotes. This leads to a local rearrangement of the 23 S rRNA that prevents peptide bond formation and accommodation of release factors. The stalled ribosome obstructs the formation of a Rho-independent terminator structure that prevents msrD transcriptional attenuation. Erythromycin induction of msrD expression via MsrDL, is suppressed by ectopic expression of mrsD, but not by mutants which do not provide antibiotic resistance, showing correlation between MsrD function in antibiotic resistance and its action on this stalled complex.
External linksNat Commun / PubMed:37393329 / PubMed Central
MethodsEM (single particle)
Resolution2.97 - 3.3 Å
Structure data

13805

7q4k

EMDB-13805, PDB-7q4k:
Erythromycin-stalled Escherichia coli 70S ribosome with streptococcal MsrDL nascent chain
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-13806: 50S LSU focused-refinement of the erythromycin-stalled Escherichia coli 70S ribosome with streptococcal MsrDL nascent chain
Method: EM (single particle) / Resolution: 2.97 Å

EMDB-13807: 30S-body SSU focused-refinement of the erythromycin-stalled Escherichia coli 70S ribosome with streptococcal MsrDL nascent chain
Method: EM (single particle) / Resolution: 3.08 Å

EMDB-13808: 30S-head SSU focused-refinement of the erythromycin-stalled Escherichia coli 70S ribosome with streptococcal MsrDL nascent chain
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ERY:
ERYTHROMYCIN A / antibiotic*YM

ChemComp-HOH:
WATER

Source
  • escherichia coli (E. coli)
  • streptococcus pneumoniae (bacteria)
  • escherichia coli k-12 (bacteria)
KeywordsRIBOSOME / protein synthesis / antibiotic resistance / ARE ABC-F protein family / leader peptide / cryo-EM

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