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Crystal structure of eIF 2B and insights into eIF 2– eIF 2B interactions
Author(s) -
Kashiwagi Kazuhiro,
Ito Takuhiro,
Yokoyama Shigeyuki
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13896
Subject(s) - initiation factor , heterotrimeric g protein , translation (biology) , protein subunit , chemistry , gtp' , biochemistry , eif2 , microbiology and biotechnology , biology , g protein , enzyme , messenger rna , signal transduction , gene
Eukaryotic translation initiation factor 2B ( eIF 2B), a heterodecameric complex of two sets of the α, β, γ, δ, and ε subunits, is the guanine nucleotide exchange factor ( GEF ) specific for eIF 2, a heterotrimeric G protein consisting of the α, β, and γ subunits. The eIF 2 protein binds GTP on the γ subunits and delivers an initiator methionyl‐ tRNA (Met‐ tRNA i Met ) to the ribosome. The GEF activity of eIF 2B is inhibited by stress‐induced phosphorylation of Ser51 in the α subunit of eIF 2, which leads to lower amounts of active eIF 2 and a limited quantity of Met‐ tRNA i M et for the ribosome, resulting in global repression of translation. However, the structural mechanism of the GEF activity inhibition remained enigmatic, and therefore the three‐dimensional structure of the entire eIF 2B molecule had been awaited. Recently, we determined the crystal structure of Schizosaccharomyces pombe eIF 2B. In this Structural Snapshot, we present the structural features of eIF 2B and the mechanism underlying the GEF activity inhibition by the phosphorylation of eIF 2α, elucidated from structure‐based in vitro analyses.