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

Dmitri N. Ermolenko, Peter V. Cornish, Taekjip Ha, Harry F. Noller

Research output: Contribution to journalArticle

Abstract

In the absence of elongation factor EF-G, ribosomes undergo spontaneous, thermally driven fluctuation between the pretranslocation (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.

Original languageEnglish (US)
Pages (from-to)158-166
Number of pages9
JournalRNA
Volume19
Issue number2
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Keywords

  • Antibiotics
  • Brownian ratchet mechanism
  • MRNA translocation
  • Ribosome

ASJC Scopus subject areas

  • Molecular Biology

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