Allosteric control of the ribosome by small-molecule antibiotics. Academic Article uri icon

Overview

MeSH

  • Crystallography, X-Ray
  • Escherichia coli Proteins
  • Models, Molecular
  • Protein Biosynthesis
  • RNA, Ribosomal
  • Ribosome Subunits, Small, Bacterial

MeSH Major

  • Anti-Bacterial Agents
  • Escherichia coli
  • Neomycin
  • RNA, Bacterial
  • RNA, Transfer, Amino Acyl
  • Ribosome Subunits, Large, Bacterial

abstract

  • Protein synthesis is targeted by numerous, chemically distinct antibiotics that bind and inhibit key functional centers of the ribosome. Using single-molecule imaging and X-ray crystallography, we show that the aminoglycoside neomycin blocks aminoacyl-transfer RNA (aa-tRNA) selection and translocation as well as ribosome recycling by binding to helix 69 (H69) of 23S ribosomal RNA within the large subunit of the Escherichia coli ribosome. There, neomycin prevents the remodeling of intersubunit bridges that normally accompanies the process of subunit rotation to stabilize a partially rotated ribosome configuration in which peptidyl (P)-site tRNA is constrained in a previously unidentified hybrid position. Direct measurements show that this neomycin-stabilized intermediate is incompatible with the translation factor binding that is required for distinct protein synthesis reactions. These findings reveal the functional importance of reversible intersubunit rotation to the translation mechanism and shed new light on the allosteric control of ribosome functions by small-molecule antibiotics.

publication date

  • September 2012

has subject area

  • Anti-Bacterial Agents
  • Crystallography, X-Ray
  • Escherichia coli
  • Escherichia coli Proteins
  • Models, Molecular
  • Neomycin
  • Protein Biosynthesis
  • RNA, Bacterial
  • RNA, Ribosomal
  • RNA, Transfer, Amino Acyl
  • Ribosome Subunits, Large, Bacterial
  • Ribosome Subunits, Small, Bacterial

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3645490

Digital Object Identifier (DOI)

  • 10.1038/nsmb.2360

PubMed ID

  • 22902368

Additional Document Info

start page

  • 957

end page

  • 963

volume

  • 19

number

  • 9