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Large-scale movement of eIF3 domains during translation initiation modulate start codon selection
The eukaryotic initiation factor 3 (eIF3) complex is involved in every step of translation initiation, but there is limited understanding of its molecular functions. Here, we present a single particle electron cryomicroscopy (cryo-EM) reconstruction of yeast 48S ribosomal preinitiation complex (PIC)...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599844/ https://www.ncbi.nlm.nih.gov/pubmed/34648019 http://dx.doi.org/10.1093/nar/gkab908 |
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author | Llácer, Jose L Hussain, Tanweer Dong, Jinsheng Villamayor, Laura Gordiyenko, Yuliya Hinnebusch, Alan G |
author_facet | Llácer, Jose L Hussain, Tanweer Dong, Jinsheng Villamayor, Laura Gordiyenko, Yuliya Hinnebusch, Alan G |
author_sort | Llácer, Jose L |
collection | PubMed |
description | The eukaryotic initiation factor 3 (eIF3) complex is involved in every step of translation initiation, but there is limited understanding of its molecular functions. Here, we present a single particle electron cryomicroscopy (cryo-EM) reconstruction of yeast 48S ribosomal preinitiation complex (PIC) in an open conformation conducive to scanning, with core subunit eIF3b bound on the 40S interface near the decoding center in contact with the ternary complex eIF2·GTP·initiator tRNA. eIF3b is relocated together with eIF3i from their solvent interface locations observed in other PIC structures, with eIF3i lacking 40S contacts. Re-processing of micrographs of our previous 48S PIC in a closed state also suggests relocation of the entire eIF3b-3i-3g-3a-Cter module during the course of initiation. Genetic analysis indicates that high fidelity initiation depends on eIF3b interactions at the 40S subunit interface that promote the closed PIC conformation, or facilitate the relocation of eIF3b/eIF3i to the solvent interface, on start codon selection. |
format | Online Article Text |
id | pubmed-8599844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-85998442021-11-18 Large-scale movement of eIF3 domains during translation initiation modulate start codon selection Llácer, Jose L Hussain, Tanweer Dong, Jinsheng Villamayor, Laura Gordiyenko, Yuliya Hinnebusch, Alan G Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The eukaryotic initiation factor 3 (eIF3) complex is involved in every step of translation initiation, but there is limited understanding of its molecular functions. Here, we present a single particle electron cryomicroscopy (cryo-EM) reconstruction of yeast 48S ribosomal preinitiation complex (PIC) in an open conformation conducive to scanning, with core subunit eIF3b bound on the 40S interface near the decoding center in contact with the ternary complex eIF2·GTP·initiator tRNA. eIF3b is relocated together with eIF3i from their solvent interface locations observed in other PIC structures, with eIF3i lacking 40S contacts. Re-processing of micrographs of our previous 48S PIC in a closed state also suggests relocation of the entire eIF3b-3i-3g-3a-Cter module during the course of initiation. Genetic analysis indicates that high fidelity initiation depends on eIF3b interactions at the 40S subunit interface that promote the closed PIC conformation, or facilitate the relocation of eIF3b/eIF3i to the solvent interface, on start codon selection. Oxford University Press 2021-10-14 /pmc/articles/PMC8599844/ /pubmed/34648019 http://dx.doi.org/10.1093/nar/gkab908 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene regulation, Chromatin and Epigenetics Llácer, Jose L Hussain, Tanweer Dong, Jinsheng Villamayor, Laura Gordiyenko, Yuliya Hinnebusch, Alan G Large-scale movement of eIF3 domains during translation initiation modulate start codon selection |
title | Large-scale movement of eIF3 domains during translation initiation modulate start codon selection |
title_full | Large-scale movement of eIF3 domains during translation initiation modulate start codon selection |
title_fullStr | Large-scale movement of eIF3 domains during translation initiation modulate start codon selection |
title_full_unstemmed | Large-scale movement of eIF3 domains during translation initiation modulate start codon selection |
title_short | Large-scale movement of eIF3 domains during translation initiation modulate start codon selection |
title_sort | large-scale movement of eif3 domains during translation initiation modulate start codon selection |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599844/ https://www.ncbi.nlm.nih.gov/pubmed/34648019 http://dx.doi.org/10.1093/nar/gkab908 |
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