July 7, 2019  |  

Sequence-dependent elongation dynamics on macrolide-bound ribosomes.

Authors: Johansson, Magnus and Chen, Jin and Tsai, Albert and Kornberg, Guy and Puglisi, Joseph D

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 or pauses 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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Journal: Cell reports
DOI: 10.1016/j.celrep.2014.04.034
Year: 2014

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