Critical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain

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dc.contributor.authorKoch, Miriam
dc.contributor.authorWilli, Jessica
dc.contributor.authorPradere, Ugo
dc.contributor.authorHall, Jonathan
dc.contributor.authorPolacek, Norbert
dc.date.accessioned2025-07-18T16:58:56Z
dc.date.available2025-07-18T16:58:56Z
dc.date.issued2017
dc.descriptionOpen access article. Creative Commons Attribution-NonCommercial 4.0 International license (CC BY-NC 4.0) applies
dc.description.abstractThe nascent peptide exit tunnel has recently been identified as a functional region of ribosomes contributing to translation regulation and co-translational protein folding. Inducible expression of the erm resistance genes depends on ribosome stalling at specific codons of an upstream open reading frame in the presence of an exit tunnel-bound macrolide antibiotic. The molecular basis for this translation arrest is still not fully understood. Here, we used a nucleotide analog interference approach to unravel important functional groups on 23S rRNA residues in the ribosomal exit tunnel for ribosome stalling on the ErmC leader peptide. By replacing single nucleobase functional groups or even single atoms we were able to demonstrate the importance of A2062, A2503 and U2586 for drug-dependent ribosome stalling. Our data show that the universally conserved A2062 and A2503 are capable of forming a non-Watson–Crick base pair that is critical for sensing and transmitting the stalling signal from the exit tunnel back to the peptidyl transferase center of the ribosome. The nucleobases of A2062, A2503 as well as U2586 do not contribute significantly to the overall mechanism of protein biosynthesis, yet their elaborate role for co-translational monitoring of nascent peptide chains inside the exit tunnel can explain their evolutionary conservation.
dc.description.peer-reviewYes
dc.identifier.citationKoch, M., Willi, J., Pradere, U., Hall, J., & Polacek, N. (2017). Critical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain. Nucleic Acids Research, 45(11), 6717-6728. https://doi.org/10.1093/nar/gkx195
dc.identifier.urihttps://hdl.handle.net/10133/7072
dc.language.isoen
dc.publisherOxford Academic
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Bern
dc.publisher.institutionInstitute of Pharmaceutical Sciences (ETH Zurich)
dc.publisher.urlhttps://doi.org/10.1093/nar/gkx195
dc.subjectrRNA
dc.subjectRibosome stalling
dc.subjectTranslation arrest
dc.subjectPeptide
dc.titleCritical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain
dc.typeArticle
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