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Title | Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts. |
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Journal, issue, pages | Cell Rep, Vol. 33, Issue 12, Page 108534, Year 2020 |
Publish date | Dec 22, 2020 |
Authors | Anthony Bochler / Jailson Brito Querido / Terezie Prilepskaja / Heddy Soufari / Angelita Simonetti / Mayara Lucia Del Cistia / Lauriane Kuhn / Aline Rimoldi Ribeiro / Leoš Shivaya Valášek / Yaser Hashem / |
PubMed 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 ...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. |
External links | Cell Rep / PubMed:33357443 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.33 - 8.1 Å |
Structure data | EMDB-11893, PDB-7ase: EMDB-11895, PDB-7ask: EMDB-11896: |
Chemicals | ChemComp-ZN: ChemComp-MG: ChemComp-GNP: ChemComp-ADP: |
Source |
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Keywords | TRANSLATION / preinitiation / factors / kinetoplastid / helicase |