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RNA. 2013 Feb;19(2):158-66. doi: 10.1261/rna.035964.112. Epub 2012 Dec 17.

Antibiotics that bind to the A site of the large ribosomal subunit can induce mRNA translocation.

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1
Department of Biochemistry and Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA. Dmitri_Ermolenko@urmc.rochester.edu

Abstract

In the absence of elongation factor EF-G, ribosomes undergo spontaneous, thermally driven fluctuation between the pre-translocation (classical) and intermediate (hybrid) states of translocation. These fluctuations do not result in productive mRNA translocation. Extending previous findings that the antibiotic sparsomycin induces translocation, we identify additional peptidyl transferase inhibitors that trigger productive mRNA translocation. We find that antibiotics that bind the peptidyl transferase A site induce mRNA translocation, whereas those that do not occupy the A site fail to induce translocation. Using single-molecule FRET, we show that translocation-inducing antibiotics do not accelerate intersubunit rotation, but act solely by converting the intrinsic, thermally driven dynamics of the ribosome into translocation. Our results support the idea that the ribosome is a Brownian ratchet machine, whose intrinsic dynamics can be rectified into unidirectional translocation by ligand binding.

PMID:
23249745
PMCID:
PMC3543091
DOI:
10.1261/rna.035964.112
[Indexed for MEDLINE]
Free PMC Article

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