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

Koch, Miriam; Willi, Jessica; Polacek, Norbert (2017). Critical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain. Nucleic acids research, 45(11), pp. 6717-6728. Oxford University Press 10.1093/nar/gkx195

[img]
Preview
Text
Koch et al_NAR_2017.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC).

Download (6MB) | Preview

The nascent peptide exit tunnel has recently been identified as a functional region of ribosomes contributing to translation regulation and cotranslational 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Koch, Miriam; Willi, Jessica and Polacek, Norbert

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0305-1048

Publisher:

Oxford University Press

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

06 Jun 2017 16:41

Last Modified:

09 Sep 2017 10:02

Publisher DOI:

10.1093/nar/gkx195

BORIS DOI:

10.7892/boris.98051

URI:

https://boris.unibe.ch/id/eprint/98051

Actions (login required)

Edit item Edit item
Provide Feedback