title: Crystal structure of eIF2B and insights into eIF2-eIF2B interactions.
abstract: Eukaryotic translation initiation factor 2B (eIF2B), a heterodecameric complex of two sets of the α, β, γ, δ, and ε subunits, is the guanine nucleotide exchange factor (GEF) specific for eIF2, a heterotrimeric G protein consisting of the α, β, and γ subunits. The eIF2 protein binds GTP on the γ subunits and delivers an initiator methionyl-tRNA (Met-tRNAiMet) to the ribosome. The GEF activity of eIF2B is inhibited by stress-induced phosphorylation of Ser51 in the α subunit of eIF2, which leads to lower amounts of active eIF2 and a limited quantity of Met-tRNAiMetfor 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 eIF2B molecule had been awaited. Recently, we determined the crystal structure of Schizosaccharomyces pombe eIF2B. In this Structural Snapshot, we present the structural features of eIF2B and the mechanism underlying the GEF activity inhibition by the phosphorylation of eIF2α, elucidated from structure-based in vitro analyses.
authors.affiliation: Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, Tsurumi-ku, Yokohama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kashiwagi
authors.affiliation: Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, Tsurumi-ku, Yokohama, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Ito
authors.affiliation: RIKEN Structural Biology Laboratory, Tsurumi-ku, Yokohama, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D015852:Eukaryotic Initiation Factor-2 / Q000737:chemistry* / Q000378:metabolism; D020717:Eukaryotic Initiation Factor-2B / Q000737:chemistry* / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry / Q000235:genetics; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics; D012568:Schizosaccharomyces / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D015852:Eukaryotic Initiation Factor-2; D020717:Eukaryotic Initiation Factor-2B; D020662:Guanine Nucleotide Exchange Factors; D012346:RNA, Transfer, Amino Acyl; C026464:tRNA(m)(Met), methionine-
keywords: X-ray crystallography; eIF2B; eukaryotic translation initiation factor; guanine nucleotide exchange factor; translational control