4ZEO

Crystal structure of eIF2B delta from Chaetomium thermophilum

4ZEO の概要

• エントリーDOI: 10.2210/pdb4zeo/pdb
• 分子名称: Translation initiation factor eif-2b-like protein (2 entities in total)
• 機能のキーワード: eif2b, eif2, guanine nucleotide exchange factor, gef, regulatory subcomplex, regulatory subunit, translation initiation, translation
• 由来する生物種: Chaetomium thermophilum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 99485.20

構造登録者

Kuhle, B.,Ficner, R. (登録日: 2015-04-20, 公開日: 2015-09-30, 最終更新日: 2024-01-10)

主引用文献

Kuhle, B.,Eulig, N.K.,Ficner, R.
Architecture of the eIF2B regulatory subcomplex and its implications for the regulation of guanine nucleotide exchange on eIF2.
Nucleic Acids Res., 43:9994-10014, 2015

PubMed Abstract: Eukaryal translation initiation factor 2B (eIF2B) acts as guanine nucleotide exchange factor (GEF) for eIF2 and forms a central target for pathways regulating global protein synthesis. eIF2B consists of five non-identical subunits (α-ϵ), which assemble into a catalytic subcomplex (γ, ϵ) responsible for the GEF activity, and a regulatory subcomplex (α, β, δ) which regulates the GEF activity under stress conditions. Here, we provide new structural and functional insight into the regulatory subcomplex of eIF2B (eIF2B(RSC)). We report the crystal structures of eIF2Bβ and eIF2Bδ from Chaetomium thermophilum as well as the crystal structure of their tetrameric eIF2B(βδ)2 complex. Combined with mutational and biochemical data, we show that eIF2B(RSC) exists as a hexamer in solution, consisting of two eIF2Bβδ heterodimers and one eIF2Bα2 homodimer, which is homologous to homohexameric ribose 1,5-bisphosphate isomerases. This homology is further substantiated by the finding that eIF2Bα specifically binds AMP and GMP as ligands. Based on our data, we propose a model for eIF2B(RSC) and its interactions with eIF2 that is consistent with previous biochemical and genetic data and provides a framework to better understand eIF2B function, the molecular basis for Gcn(-), Gcd(-) and VWM/CACH mutations and the evolutionary history of the eIF2B complex.

PubMed: 26384431
DOI: 10.1093/nar/gkv930

実験手法

X-RAY DIFFRACTION (2.55 Å)