Sequence-dependent elongation dynamics on macrolide-bound ribosomes.

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 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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Johansson M,Chen J,Tsai A,Kornberg G,Puglisi JD

doi

10.1016/j.celrep.2014.04.034

subject

Has Abstract

pub_date

2014-06-12 00:00:00

pages

1534-1546

issue

5

issn

2211-1247

pii

S2211-1247(14)00336-2

journal_volume

7

pub_type

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