AI Article Synopsis

  • The formation of the 43S pre-initiation complex (PIC) is crucial for canonical mRNA translation in eukaryotes, involving initiator Met-tRNA and several eukaryotic initiation factors (eIFs) bound to the small ribosomal subunit (40S).
  • Structural differences in the 40S ribosomal subunit of trypanosomatids, like Trypanosoma cruzi (the cause of Chagas disease), indicate variability in translation initiation compared to mammals.
  • The study reveals unique features of the 43S PIC structure, including a distinct eIF3 structure, interactions with rRNA expansion segments, and the role of a kinetoplastid-specific helicase, supported by biochemical assays and mass spect

Article Abstract

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773551PMC
http://dx.doi.org/10.1016/j.celrep.2020.108534DOI Listing

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