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Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts
Canonical mRNA translation in eukaryotes begins with the formation of the 43S pre-initiation complex (PIC). Its assembly requires binding of initiator Met-tRNA(i)(Met) and several eukaryotic initiation factors (eIFs) to the small ribosomal subunit (40S). Compared to their mammalian hosts, trypanosom...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773551/ https://www.ncbi.nlm.nih.gov/pubmed/33357443 http://dx.doi.org/10.1016/j.celrep.2020.108534 |
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author | Bochler, Anthony Querido, Jailson Brito Prilepskaja, Terezie Soufari, Heddy Simonetti, Angelita Del Cistia, Mayara Lucia Kuhn, Lauriane Ribeiro, Aline Rimoldi Valášek, Leoš Shivaya Hashem, Yaser |
author_facet | Bochler, Anthony Querido, Jailson Brito Prilepskaja, Terezie Soufari, Heddy Simonetti, Angelita Del Cistia, Mayara Lucia Kuhn, Lauriane Ribeiro, Aline Rimoldi Valášek, Leoš Shivaya Hashem, Yaser |
author_sort | Bochler, Anthony |
collection | PubMed |
description | Canonical mRNA translation in eukaryotes begins with the formation of the 43S pre-initiation complex (PIC). Its assembly requires binding of initiator Met-tRNA(i)(Met) 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(S), 7(S), and 6(S), 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. |
format | Online Article Text |
id | pubmed-7773551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77735512021-01-05 Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts Bochler, Anthony Querido, Jailson Brito Prilepskaja, Terezie Soufari, Heddy Simonetti, Angelita Del Cistia, Mayara Lucia Kuhn, Lauriane Ribeiro, Aline Rimoldi Valášek, Leoš Shivaya Hashem, Yaser Cell Rep Article Canonical mRNA translation in eukaryotes begins with the formation of the 43S pre-initiation complex (PIC). Its assembly requires binding of initiator Met-tRNA(i)(Met) 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(S), 7(S), and 6(S), 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. Cell Press 2020-12-22 /pmc/articles/PMC7773551/ /pubmed/33357443 http://dx.doi.org/10.1016/j.celrep.2020.108534 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Bochler, Anthony Querido, Jailson Brito Prilepskaja, Terezie Soufari, Heddy Simonetti, Angelita Del Cistia, Mayara Lucia Kuhn, Lauriane Ribeiro, Aline Rimoldi Valášek, Leoš Shivaya Hashem, Yaser Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts |
title | Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts |
title_full | Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts |
title_fullStr | Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts |
title_full_unstemmed | Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts |
title_short | Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts |
title_sort | structural differences in translation initiation between pathogenic trypanosomatids and their mammalian hosts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773551/ https://www.ncbi.nlm.nih.gov/pubmed/33357443 http://dx.doi.org/10.1016/j.celrep.2020.108534 |
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