Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts.
Fiche publication
Date publication
décembre 2020
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SIMONETTI Angelita
Tous les auteurs :
Bochler A, Querido JB, Prilepskaja T, Soufari H, Simonetti A, Del Cistia ML, Kuhn L, Ribeiro AR, Valášek LS, Hashem Y
Lien Pubmed
Résumé
Canonical mRNA translation in eukaryotes begins with the formation of the 43S pre-initiation complex (PIC). Its assembly requires binding of initiator Met-tRNA and several eukaryotic initiation factors (eIFs) to the small ribosomal subunit (40S). Compared to their mammalian hosts, trypanosomatids present significant structural differences in their 40S, suggesting substantial variability in translation initiation. Here, we determine the structure of the 43S PIC from Trypanosoma cruzi, the parasite causing Chagas disease. Our structure shows numerous specific features, such as the variant eIF3 structure and its unique interactions with the large rRNA expansion segments (ESs) 9, 7, and 6, and the association of a kinetoplastid-specific DDX60-like helicase. It also reveals the 40S-binding site of the eIF5 C-terminal domain and structures of key terminal tails of several conserved eIFs underlying their activities within the PIC. Our results are corroborated by glutathione S-transferase (GST) pull-down assays in both human and T. cruzi and mass spectrometry data.
Mots clés
ES6(S), ES7(S), ES9(S), Trypanosoma cruzi, cryo-EM, eIF1, eIF2, eIF3, eIF5-CTD, k-DDX60, the 43S pre-initiation complex, translation initiation
Référence
Cell Rep. 2020 Dec 22;33(12):108534