Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine

Elife. 2014 Jun 9;3:e03080. doi: 10.7554/eLife.03080.


Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as potential anti-malarial therapies. Antibiotics that inhibit protein translation are promising candidates for repositioning. We have solved the cryo-EM structure of the cytoplasmic ribosome from the human malaria parasite, Plasmodium falciparum, in complex with emetine at 3.2 Å resolution. Emetine is an anti-protozoan drug used in the treatment of ameobiasis that also displays potent anti-malarial activity. Emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin, thereby delivering its therapeutic effect by blocking mRNA/tRNA translocation. As the first cryo-EM structure that visualizes an antibiotic bound to any ribosome at atomic resolution, this establishes cryo-EM as a powerful tool for screening and guiding the design of drugs that target parasite translation machinery.

Keywords: Plasmodium falciparum; biophysics; cryo-EM; drug development; malaria; ribosome; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemistry
  • Binding Sites
  • Cryoelectron Microscopy
  • Cytoplasm / metabolism
  • Drug Design
  • Emetine / chemistry*
  • Erythrocytes / parasitology
  • Humans
  • Models, Molecular
  • Pactamycin / chemistry
  • Plasmodium falciparum / metabolism*
  • Protein Binding
  • RNA, Messenger / metabolism
  • Ribosomal Proteins / chemistry
  • Ribosomes / chemistry*
  • Ribosomes / ultrastructure*


  • Antimalarials
  • RNA, Messenger
  • Ribosomal Proteins
  • Pactamycin
  • Emetine