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 language | English (US) |
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Pages (from-to) | 1534-1546 |
Number of pages | 13 |
Journal | Cell Reports |
Volume | 7 |
Issue number | 5 |
DOIs | |
State | Published - Jun 12 2014 |
Externally published | Yes |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology