eIF2 interactions with initiator tRNA and eIF2B are regulated by post-translational modifications and conformational dynamics

Translation of messenger RNA (mRNA) into proteins is key to eukaryotic gene expression and begins when initiation factor-2 (eIF2) delivers methionyl initiator tRNA (Met-tRNA i Met ) to ribosomes. This first step is controlled by eIF2B mediating guanine nucleotide exchange on eIF2. We isolated eIF2 f...

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Veröffentlicht in:Cell discovery 2015-08, Vol.1 (1), p.15020-15020, Article 15020
Hauptverfasser: Beilsten-Edmands, Victoria, Gordiyenko, Yuliya, Kung, Jocky CK, Mohammed, Shabaz, Schmidt, Carla, Robinson, Carol V
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container_issue 1
container_start_page 15020
container_title Cell discovery
container_volume 1
creator Beilsten-Edmands, Victoria
Gordiyenko, Yuliya
Kung, Jocky CK
Mohammed, Shabaz
Schmidt, Carla
Robinson, Carol V
description Translation of messenger RNA (mRNA) into proteins is key to eukaryotic gene expression and begins when initiation factor-2 (eIF2) delivers methionyl initiator tRNA (Met-tRNA i Met ) to ribosomes. This first step is controlled by eIF2B mediating guanine nucleotide exchange on eIF2. We isolated eIF2 from yeast and used mass spectrometry to study the intact complex, and found that eIF2β is the most labile of the three subunits (eIF2α/β/γ). We then compared conformational dynamics of the ternary complex eIF2:GTP:Met-tRNA i Met with apo eIF2 using comparative chemical cross-linking. Results revealed high conformational dynamics for eIF2α in apo eIF2 while in the ternary complex all three subunits are constrained. Novel post-translational modifications identified here in both eIF2 and eIF2B were combined with established sites, and located within protein sequences and homology models. We found clustering at subunit interfaces and highly phosphorylated unstructured regions, at the N-terminus of eIF2β, and also between the eIF2Bε core and catalytic domains. We propose that modifications of these unstructured regions have a key role in regulating interactions between eIF2 and eIF2B, as well as other eIFs.
doi_str_mv 10.1038/celldisc.2015.20
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subjects Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell Cycle Analysis
Cell Physiology
Life Sciences
Stem Cells
title eIF2 interactions with initiator tRNA and eIF2B are regulated by post-translational modifications and conformational dynamics
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