7ASK

43S preinitiation complex from Trypanosoma cruzi with the kDDX60 helicase bound with ATP

Summary for 7ASK

• Entry DOI: 10.2210/pdb7ask/pdb
• Related: 7ASE
• EMDB information: 11893 11895
• Descriptor: kDDX60, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: preinitiation, factors, kinetoplastid, helicase, translation
• Biological source: Trypanosoma cruzi
• Total number of polymer chains: 1
• Total formula weight: 247201.38

Authors

Bochler, A.,Brito Querido, J.,Prilepskaja, T.,Soufari, H.,Del Cistia, M.L.,Kuhn, L.,Rimoldi Ribeiro, A.,Valasek, L.S.,Hashem, Y. (deposition date: 2020-10-27, release date: 2021-04-14, Last modification date: 2024-05-01)

Primary citation

Bochler, A.,Querido, J.B.,Prilepskaja, T.,Soufari, H.,Simonetti, A.,Del Cistia, M.L.,Kuhn, L.,Ribeiro, A.R.,Valasek, L.S.,Hashem, Y.
Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts.
Cell Rep, 33:108534-108534, 2020

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 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.

PubMed: 33357443
DOI: 10.1016/j.celrep.2020.108534

Experimental method

ELECTRON MICROSCOPY (4.3 Å)