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-Structure paper
Title | Drug sensing by the ribosome induces translational arrest via active site perturbation. |
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Journal, issue, pages | Mol Cell, Vol. 56, Issue 3, Page 446-452, Year 2014 |
Publish date | Nov 6, 2014 |
Authors | Stefan Arenz / Sezen Meydan / Agata L Starosta / Otto Berninghausen / Roland Beckmann / Nora Vázquez-Laslop / Daniel N Wilson / |
PubMed Abstract | During protein synthesis, nascent polypeptide chains within the ribosomal tunnel can act in cis to induce ribosome stalling and regulate expression of downstream genes. The Staphylococcus aureus ...During protein synthesis, nascent polypeptide chains within the ribosomal tunnel can act in cis to induce ribosome stalling and regulate expression of downstream genes. The Staphylococcus aureus ErmCL leader peptide induces stalling in the presence of clinically important macrolide antibiotics, such as erythromycin, leading to the induction of the downstream macrolide resistance methyltransferase ErmC. Here, we present a cryo-electron microscopy (EM) structure of the erythromycin-dependent ErmCL-stalled ribosome at 3.9 Å resolution. The structure reveals how the ErmCL nascent chain directly senses the presence of the tunnel-bound drug and thereby induces allosteric conformational rearrangements at the peptidyltransferase center (PTC) of the ribosome. ErmCL-induced perturbations of the PTC prevent stable binding and accommodation of the aminoacyl-tRNA at the A-site, leading to inhibition of peptide bond formation and translation arrest. |
External links | Mol Cell / PubMed:25306253 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.9 Å |
Structure data | |
Chemicals | ChemComp-ERY: |
Source |
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Keywords | RIBOSOME/ANTIBIOTIC / erythromycin / stalling / RIBOSOME-ANTIBIOTIC complex |