We released our first preprint as a lab, and it’s a big one!

Summary

Malaria parasites rely heavily on rapid, high fidelity protein synthesis to infect human erythrocytes, making translation an attractive target for new antimalarials. Here, we determined in situ structures of Pf80S ribosomes in thirteen conformational and compositional states from cryoFIB-milled Plasmodium falciparum-infected human erythrocytes across the stages of asexual intraerythrocytic parasite replication.

Our work reveals new insights into translation in the native cellular context that were not possible to achieve with single-particle cryoEM structures, including a bifurcated translation elongation cycle that may represent a general but as-yet-undescribed feature of translation. We resolve a long-standing controversy in the field regarding the mysterious absence of PfRACK1 in published single-particle structures of the Pf80S ribosome, and provide valuable insight into the mode of action and cellular consequences of disrupting malarial translation with a top antimalarial drug candidate.

We’re incredibly proud of this massive team effort. Check it out!