Context-specific action of macrolide antibiotics on the eukaryotic ribosome

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F21%3A00124436" target="_blank" >RIV/00216224:14740/21:00124436 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41467-021-23068-1" target="_blank" >https://www.nature.com/articles/s41467-021-23068-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-021-23068-1" target="_blank" >10.1038/s41467-021-23068-1</a>

Result language

angličtina

Original language name

Context-specific action of macrolide antibiotics on the eukaryotic ribosome

Original language description

Macrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of proteins. Because preventing translation of individual proteins could be beneficial for the treatment of human diseases, we asked whether macrolides, if bound to the eukaryotic ribosome, would retain their context- and protein-specific action. By introducing a single mutation in rRNA, we rendered yeast Saccharomyces cerevisiae cells sensitive to macrolides. Cryo-EM structural analysis showed that the macrolide telithromycin binds in the tunnel of the engineered eukaryotic ribosome. Genome-wide analysis of cellular translation and biochemical studies demonstrated that the drug inhibits eukaryotic translation by preferentially stalling ribosomes at distinct sequence motifs. Context-specific action markedly depends on the macrolide structure. Eliminating macrolide-arrest motifs from a protein renders its translation macrolide-tolerant. Our data illuminate the prospects of adapting macrolides for protein-selective translation inhibition in eukaryotic cells. Macrolide antibiotics inhibit bacterial translation in a context-specific manner, arresting ribosomes at defined sites within mRNAs and selectively inhibiting synthesis of only a subset of cellular proteins. Here the authors provide a structural basis for the context-specific activity of macrolides on the eukaryotic ribosome.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

—

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

14

Pages from-to

2803

UT code for WoS article

000658675200003

EID of the result in the Scopus database

2-s2.0-85105908577