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

Wilson Wong, Xiao-chen Bai, Alan Brown, Israel S Fernandez, Eric Hanssen, Melanie Condron, Yan Hong Tan, Jake Baum, Sjors HW Scheres
  • eLife, June 2014, eLife
  • DOI: 10.7554/elife.03080

Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to a candidate anti-malarial drug

What is it about?

High resolution structure determination of macromolecules traditionally requires the crystallisation and subsequent analysis of the X-ray diffraction data of the molecules of interest. Here, we have bypassed these barriers by applying recent advances in cryo-EM data collection and statistical image analyses to solve the structure of the Plasmodium falciparum 80S ribosome to atomic resolution, along with molecular details of a bound, candidate anti-malarial drug emetine.

Why is it important?

This study illustrates the potential of modern cryo-EM in visualising drugs that target the parasite translation machinery. Low yield in ribosome material and sample heterogeneity are no longer a hinderance to structure determination. The structural detail of Pf80S-emetine interaction can be used to improve the medicinal property of emetine. Moreover, structural differences between human and parasite 80S ribosomes can be exploited for specific inhibition of parasite protein synthesis.

The following have contributed to this page: Xiaochen Bai, Sjors Scheres, and Dr Wilson Wong