Sequence-dependent elongation dynamics on macrolide-bound ribosomes

Magnus Johansson, Jin Chen, Albert Tsai, Guy Kornberg, Joseph D. Puglisi

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The traditional view of macrolide antibiotics as plugs inside the ribosomal nascent peptide exit tunnel (NPET) has lately been challenged in favor of a more complex, heterogeneous mechanism, where drug-peptide interactions determine the fate of a translating ribosome. To investigate these highly dynamic processes, we applied single-molecule tracking of elongating ribosomes during inhibition of elongation by erythromycin of several nascent chains, including ErmCL and H-NS, which were shown to be, respectively, sensitive and resistant to erythromycin. Peptide sequence-specific changes were observed in translation elongation dynamics in the presence of a macrolide-obstructed NPET. Elongation rates were not severely inhibited in general by the presence of the drug; instead, stalls orpauses were observed as abrupt events. The dynamic pathways of nascent-chain-dependent elongation pausing in the presence of macrolides determine the fate of the translating ribosome stalling or readthrough.

Original languageEnglish (US)
Pages (from-to)1534-1546
Number of pages13
JournalCell Reports
Volume7
Issue number5
DOIs
StatePublished - Jun 12 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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