Inhibition of antiassociation activity of translation initiation factor 3 by paromomycin

Go Hirokawa1, Hideko Kaji, Akira Kaji

  • 1Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, 1020 Locust Street, JAH 456A, Philadelphia, PA 19107, USA.

Insights

Paromomycin antibiotic disrupts bacterial ribosome assembly by preventing initiation factor 3 (IF3) from dissociating ribosomal subunits. This stabilization of 70S ribosomes contributes to paromomycin's inhibitory effects.

Area of Science:

  • Molecular Biology
  • Microbiology
  • Biochemistry

Background:

  • Ribosome biogenesis is crucial for protein synthesis in bacteria.
  • Initiation factor 3 (IF3) plays a key role in regulating ribosomal subunit association and dissociation.
  • Paromomycin is an aminoglycoside antibiotic that inhibits bacterial protein synthesis.

Purpose of the Study:

  • To investigate the effect of paromomycin on the interaction between ribosomal subunits.
  • To elucidate the mechanism by which paromomycin affects the function of initiation factor 3 (IF3).

Main Methods:

  • Studying the antiassociation activity of IF3 in the presence of paromomycin.
  • Observing the association of ribosomal subunits to form 70S ribosomes under varying conditions.
  • Analyzing the binding and expulsion of IF3 from 30S ribosomal subunits.

Main Results:

  • Paromomycin inhibited the antiassociation activity of IF3.
  • Paromomycin promoted the association of ribosomal subunits into 70S ribosomes, even with low Mg(2+) concentrations.
  • IF3 bound to 30S subunits was expelled upon paromomycin-induced 70S ribosome formation.

Conclusions:

  • Paromomycin stabilizes 70S ribosome formation.
  • This stabilization mechanism contributes to paromomycin's inhibition of translocation and ribosome recycling.
  • Paromomycin's effects on ribosome dynamics offer insights into its antibiotic action.

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