ジャーナル: Structure / 年: 2025 タイトル: Antimalarial drug artemisinin stabilizes PfRACK1 binding to the ribosome. 著者: Ka Diam Go / Xin-Fu Yan / Grennady Wirjanata / Rya Ero / Samuel Pazicky / Jerzy Dziekan / Seth Tjia / Julien Lescar / Zbynek Bozdech / Yong-Gui Gao / 要旨: Artemisinin and its derivatives represent the core agents in artemisinin combination therapies that are the current frontline treatment for P. falciparum and P. vivax malaria infections. Artemisinins ...Artemisinin and its derivatives represent the core agents in artemisinin combination therapies that are the current frontline treatment for P. falciparum and P. vivax malaria infections. Artemisinins are known to bind a wide array of proteins that disrupt the parasite's cellular physiology. Here, we show that artemisinins' cytotoxic activity involves structural alteration of key P. falciparum macromolecular complexes, including the ribosome, proteasome, and T-complex. The structural analysis revealed that, following artemisinin treatment, a larger population of Pf80S ribosomes binds PfRACK1. Unlike in most eukaryotes, PfRACK1 does not interact with the C-terminal tail of the r-protein uS3 that in Plasmodium is truncated. This likely suggests an evolved role of uS3 in facilitating RACK1-mediated translational regulation, which would potentially benefit the parasite under certain conditions. Stabilization of RACK1 ribosome interaction likely contributes to artemisinins' mode of action.