Dynamical features of the Plasmodium falciparum ribosome during translation

Human malaria disease, caused by the eukaryotic parasite Plasmodium, is one of the most devastating infectious diseases worldwide. One promising avenue of research is suggested by the success of a few antibiotics, which inhibit the general translation process in the parasite, being used in the clinical treatment of malaria. In our group, we investigate the molecular mechanism of translation on the P. falciparum ribosome, by using cryo-electron microscopy (cryo-EM) and single-particle reconstruction. Taking advantages of these methods we were able to visualize several structures co-existing in the sample, at a resolution sufficient for building atomic models. Specifically, we obtained five cryo-EM reconstructions of ribosomes purified from P. falciparum blood-stage schizonts, distinguished both by conformation and composition. We generated an atomic model for each of these complexes, and discovered structural and dynamic features that distinguish the ribosomes of P. falciparum from those of humans. Interestingly, RACK1, a necessary ribosomal protein in eukaryotes, is absent in all P. falciparum ribosome complexes reconstructed. By biochemical techniques, we found that, indeed, RACK1 does not specifically co-purify with the 80S fraction at the P. falciparum schizonts stage and would therefore mainly function in a ribosome-unbound state in the cell. More extensive studies, using the cryo-EM methodology, of translation in the parasite will provide structural knowledge that could help in the design of effective anti-malaria drugs.

 

Reference

Sun, M., Li, W., Blomqvist, K., Das, S., Hashem, Y., Dvorin, J.D. and Frank, J. (2015) Dynamical features of the Plasmodium falciparum ribosome during translation. Nucleic Acids Res, gkv991.

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