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eIF2B is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core

eIF2B facilitates and controls protein synthesis in eukaryotes by mediating guanine nucleotide exchange on its partner eIF2. We combined mass spectrometry (MS) with chemical cross-linking, surface accessibility measurements and homology modelling to define subunit stoichiometry and interactions with...

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Autores principales: Gordiyenko, Yuliya, Schmidt, Carla, Jennings, Martin D., Matak-Vinkovic, Dijana, Pavitt, Graham D., Robinson, Carol V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046112/
https://www.ncbi.nlm.nih.gov/pubmed/24852487
http://dx.doi.org/10.1038/ncomms4902
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author Gordiyenko, Yuliya
Schmidt, Carla
Jennings, Martin D.
Matak-Vinkovic, Dijana
Pavitt, Graham D.
Robinson, Carol V.
author_facet Gordiyenko, Yuliya
Schmidt, Carla
Jennings, Martin D.
Matak-Vinkovic, Dijana
Pavitt, Graham D.
Robinson, Carol V.
author_sort Gordiyenko, Yuliya
collection PubMed
description eIF2B facilitates and controls protein synthesis in eukaryotes by mediating guanine nucleotide exchange on its partner eIF2. We combined mass spectrometry (MS) with chemical cross-linking, surface accessibility measurements and homology modelling to define subunit stoichiometry and interactions within eIF2B and eIF2. Although it is generally accepted that eIF2B is a pentamer of five non-identical subunits (α–ε), here we show that eIF2B is a decamer. MS and cross-linking of eIF2B complexes allows us to propose a model for the subunit arrangements within eIF2B where the subunit assembly occurs through catalytic γ- and ε-subunits, with regulatory subunits arranged in asymmetric trimers associated with the core. Cross-links between eIF2 and eIF2B allow modelling of interactions that contribute to nucleotide exchange and its control by eIF2 phosphorylation. Finally, we identify that GTP binds to eIF2Bγ, prompting us to propose a multi-step mechanism for nucleotide exchange.
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spelling pubmed-40461122014-06-13 eIF2B is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core Gordiyenko, Yuliya Schmidt, Carla Jennings, Martin D. Matak-Vinkovic, Dijana Pavitt, Graham D. Robinson, Carol V. Nat Commun Article eIF2B facilitates and controls protein synthesis in eukaryotes by mediating guanine nucleotide exchange on its partner eIF2. We combined mass spectrometry (MS) with chemical cross-linking, surface accessibility measurements and homology modelling to define subunit stoichiometry and interactions within eIF2B and eIF2. Although it is generally accepted that eIF2B is a pentamer of five non-identical subunits (α–ε), here we show that eIF2B is a decamer. MS and cross-linking of eIF2B complexes allows us to propose a model for the subunit arrangements within eIF2B where the subunit assembly occurs through catalytic γ- and ε-subunits, with regulatory subunits arranged in asymmetric trimers associated with the core. Cross-links between eIF2 and eIF2B allow modelling of interactions that contribute to nucleotide exchange and its control by eIF2 phosphorylation. Finally, we identify that GTP binds to eIF2Bγ, prompting us to propose a multi-step mechanism for nucleotide exchange. Nature Pub. Group 2014-05-23 /pmc/articles/PMC4046112/ /pubmed/24852487 http://dx.doi.org/10.1038/ncomms4902 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
spellingShingle Article
Gordiyenko, Yuliya
Schmidt, Carla
Jennings, Martin D.
Matak-Vinkovic, Dijana
Pavitt, Graham D.
Robinson, Carol V.
eIF2B is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core
title eIF2B is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core
title_full eIF2B is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core
title_fullStr eIF2B is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core
title_full_unstemmed eIF2B is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core
title_short eIF2B is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core
title_sort eif2b is a decameric guanine nucleotide exchange factor with a γ(2)ε(2) tetrameric core
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046112/
https://www.ncbi.nlm.nih.gov/pubmed/24852487
http://dx.doi.org/10.1038/ncomms4902
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