7Q4K

Erythromycin-stalled Escherichia coli 70S ribosome with streptococcal MsrDL nascent chain

This is a non-PDB format compatible entry.

Summary for 7Q4K

• Entry DOI: 10.2210/pdb7q4k/pdb
• Related: 6TBV
• EMDB information: 13805
• Descriptor: 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (59 entities in total)
• Functional Keywords: ribosome, protein synthesis, antibiotic resistance, are abc-f protein family, leader peptide, cryo-em
• Biological source: Escherichia coli; More
• Total number of polymer chains: 56
• Total formula weight: 2196094.01

Authors

Fostier, C.R.,Ousalem, F.,Soufari, H.,Leroy, E.C.,Ngo, S.,Innis, A.,Hashem, Y.,Boel, G. (deposition date: 2021-10-31, release date: 2022-11-16, Last modification date: 2024-04-24)

Primary citation

Fostier, C.R.,Ousalem, F.,Leroy, E.C.,Ngo, S.,Soufari, H.,Innis, C.A.,Hashem, Y.,Boel, G.
Regulation of the macrolide resistance ABC-F translation factor MsrD.
Nat Commun, 14:3891-3891, 2023

PubMed Abstract: 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.

PubMed: 37393329
DOI: 10.1038/s41467-023-39553-8

Experimental method

ELECTRON MICROSCOPY (3 Å)