Fail-safe control of translation initiation by dissociation of eIF2α phosphorylated ternary complexes

• DOI: 10.7554/elife.24542
• Publication Date: 2017-03-18T13:00:20Z
• Authors: Martin D Jennings; Christopher J Ker...; Tomas Adomavicius; Graham D Pavitt
• Keywords: eIF2; Eukaryotic translation; Ternary complex; Integrated stress response

Phosphorylation of eIF2α controls translation initiation by restricting the levels active eIF2-GTP/Met-tRNAi ternary complexes (TC). This modulates expression all eukaryotic mRNAs and contributes to cellular integrated stress response. Key controlling activity eIF2 are factors eIF2B eIF5, thought primarily function with eIF2-GDP TC respectively. Using a steady-state kinetics approach purified proteins we demonstrate that binds equal affinity irrespective presence or absence competing guanine nucleotides. We show can compete Met-tRNAi for eIF2-GTP destabilize TC. When is formed unphosphorylated eIF2, eIF5 out-compete stabilize TC/eIF5 complexes. However when phosphorylated outcompetes destabilizes These data uncover competition between identify intermediate be inhibited eIF2B.