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eIF2B is a decameric guanine nucleotide exchange factor with a γ2ε2 tetrameric core
Yuliya Gordiyenko1, Carla Schmidt2, Martin D Jennings3
11] Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK [2] MRC Laboratory of Molecular Biology, University of Cambridge, Francis Crick Avenue, Cambridge CB2 0QH, UK [3].
Nature Communications
|May 24, 2014
Summary
The eukaryotic translation initiation factor 2B (eIF2B) is a decamer, not a pentamer, with a novel subunit arrangement. This finding reveals a multi-step mechanism for guanine nucleotide exchange, crucial for controlling protein synthesis.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- Eukaryotic translation initiation factor 2B (eIF2B) is essential for protein synthesis.
- eIF2B mediates guanine nucleotide exchange on eIF2, a critical step in translation.
- The exact subunit stoichiometry and arrangement of eIF2B have been debated.
Purpose of the Study:
- To determine the precise subunit stoichiometry and arrangement of the eIF2B complex.
- To model the interactions between eIF2B and eIF2.
- To elucidate the mechanism of guanine nucleotide exchange mediated by eIF2B.
Main Methods:
- Mass spectrometry (MS) combined with chemical cross-linking.
- Surface accessibility measurements.
- Homology modelling.
Main Results:
- eIF2B exists as a decamer, challenging the previously accepted pentameric model.
- A model for eIF2B subunit arrangement was proposed, involving catalytic core subunits and regulatory subunits in asymmetric trimers.
- Interactions between eIF2 and eIF2B were modelled, explaining nucleotide exchange and its regulation by eIF2 phosphorylation.
- Guanine triphosphate (GTP) was identified to bind to the eIF2Bγ subunit.
Conclusions:
- The study redefines eIF2B as a decamer with a complex subunit organization.
- A detailed model of eIF2B structure and its interaction with eIF2 provides insights into translation regulation.
- A novel multi-step mechanism for guanine nucleotide exchange, initiated by GTP binding to eIF2Bγ, was proposed.
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