Cargando…
Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly
Translation initiation factor eIF3 acts as the key orchestrator of the canonical initiation pathway in eukaryotes, yet its structure is greatly unexplored. We report the 2.2 Å resolution crystal structure of the complex between the yeast seven-bladed β-propeller eIF3i/TIF34 and a C-terminal α-helix...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3300007/ https://www.ncbi.nlm.nih.gov/pubmed/22090426 http://dx.doi.org/10.1093/nar/gkr765 |
_version_ | 1782226191065808896 |
---|---|
author | Herrmannová, Anna Daujotytė, Dalia Yang, Ji-Chun Cuchalová, Lucie Gorrec, Fabrice Wagner, Susan Dányi, István Lukavsky, Peter J. Shivaya Valášek, Leoš |
author_facet | Herrmannová, Anna Daujotytė, Dalia Yang, Ji-Chun Cuchalová, Lucie Gorrec, Fabrice Wagner, Susan Dányi, István Lukavsky, Peter J. Shivaya Valášek, Leoš |
author_sort | Herrmannová, Anna |
collection | PubMed |
description | Translation initiation factor eIF3 acts as the key orchestrator of the canonical initiation pathway in eukaryotes, yet its structure is greatly unexplored. We report the 2.2 Å resolution crystal structure of the complex between the yeast seven-bladed β-propeller eIF3i/TIF34 and a C-terminal α-helix of eIF3b/PRT1, which reveals universally conserved interactions. Mutating these interactions displays severe growth defects and eliminates association of eIF3i/TIF34 and strikingly also eIF3g/TIF35 with eIF3 and 40S subunits in vivo. Unexpectedly, 40S-association of the remaining eIF3 subcomplex and eIF5 is likewise destabilized resulting in formation of aberrant pre-initiation complexes (PICs) containing eIF2 and eIF1, which critically compromises scanning arrest on mRNA at its AUG start codon suggesting that the contacts between mRNA and ribosomal decoding site are impaired. Remarkably, overexpression of eIF3g/TIF35 suppresses the leaky scanning and growth defects most probably by preventing these aberrant PICs to form. Leaky scanning is also partially suppressed by eIF1, one of the key regulators of AUG recognition, and its mutant sui1(G107R) but the mechanism differs. We conclude that the C-terminus of eIF3b/PRT1 orchestrates co-operative recruitment of eIF3i/TIF34 and eIF3g/TIF35 to the 40S subunit for a stable and proper assembly of 48S pre-initiation complexes necessary for stringent AUG recognition on mRNAs. |
format | Online Article Text |
id | pubmed-3300007 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33000072012-03-13 Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly Herrmannová, Anna Daujotytė, Dalia Yang, Ji-Chun Cuchalová, Lucie Gorrec, Fabrice Wagner, Susan Dányi, István Lukavsky, Peter J. Shivaya Valášek, Leoš Nucleic Acids Res Structural Biology Translation initiation factor eIF3 acts as the key orchestrator of the canonical initiation pathway in eukaryotes, yet its structure is greatly unexplored. We report the 2.2 Å resolution crystal structure of the complex between the yeast seven-bladed β-propeller eIF3i/TIF34 and a C-terminal α-helix of eIF3b/PRT1, which reveals universally conserved interactions. Mutating these interactions displays severe growth defects and eliminates association of eIF3i/TIF34 and strikingly also eIF3g/TIF35 with eIF3 and 40S subunits in vivo. Unexpectedly, 40S-association of the remaining eIF3 subcomplex and eIF5 is likewise destabilized resulting in formation of aberrant pre-initiation complexes (PICs) containing eIF2 and eIF1, which critically compromises scanning arrest on mRNA at its AUG start codon suggesting that the contacts between mRNA and ribosomal decoding site are impaired. Remarkably, overexpression of eIF3g/TIF35 suppresses the leaky scanning and growth defects most probably by preventing these aberrant PICs to form. Leaky scanning is also partially suppressed by eIF1, one of the key regulators of AUG recognition, and its mutant sui1(G107R) but the mechanism differs. We conclude that the C-terminus of eIF3b/PRT1 orchestrates co-operative recruitment of eIF3i/TIF34 and eIF3g/TIF35 to the 40S subunit for a stable and proper assembly of 48S pre-initiation complexes necessary for stringent AUG recognition on mRNAs. Oxford University Press 2012-03 2011-11-15 /pmc/articles/PMC3300007/ /pubmed/22090426 http://dx.doi.org/10.1093/nar/gkr765 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Structural Biology Herrmannová, Anna Daujotytė, Dalia Yang, Ji-Chun Cuchalová, Lucie Gorrec, Fabrice Wagner, Susan Dányi, István Lukavsky, Peter J. Shivaya Valášek, Leoš Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly |
title | Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly |
title_full | Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly |
title_fullStr | Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly |
title_full_unstemmed | Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly |
title_short | Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly |
title_sort | structural analysis of an eif3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3300007/ https://www.ncbi.nlm.nih.gov/pubmed/22090426 http://dx.doi.org/10.1093/nar/gkr765 |
work_keys_str_mv | AT herrmannovaanna structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly AT daujotytedalia structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly AT yangjichun structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly AT cuchalovalucie structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly AT gorrecfabrice structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly AT wagnersusan structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly AT danyiistvan structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly AT lukavskypeterj structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly AT shivayavalasekleos structuralanalysisofaneif3subcomplexrevealsconservedinteractionsrequiredforastableandpropertranslationpreinitiationcomplexassembly |