7L70

The eukaryotic translation initiation factor 2B from Homo sapiens in its apo form

7L70 の概要

• エントリーDOI: 10.2210/pdb7l70/pdb
• EMDBエントリー: 23209
• 分子名称: Translation initiation factor eIF-2B subunit epsilon, Translation initiation factor eIF-2B subunit beta, Translation initiation factor eIF-2B subunit delta, ... (5 entities in total)
• 機能のキーワード: translation, integrated stress response
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 530257.49

構造登録者

Wang, L.,Schoof, M.,Lawrence, R.,Boone, M.,Frost, A.,Walter, P. (登録日: 2020-12-24, 公開日: 2021-03-24, 最終更新日: 2024-03-06)

主引用文献

Schoof, M.,Boone, M.,Wang, L.,Lawrence, R.,Frost, A.,Walter, P.
eIF2B conformation and assembly state regulates the integrated stress response.
Elife, 10:-, 2021

PubMed Abstract: The integrated stress response (ISR) is activated by phosphorylation of the translation initiation factor eIF2 in response to various stress conditions. Phosphorylated eIF2 (eIF2-P) inhibits eIF2's nucleotide exchange factor eIF2B, a twofold symmetric heterodecamer assembled from subcomplexes. Here, we monitor and manipulate eIF2B assembly in vitro and in vivo. In the absence of eIF2B's α-subunit, the ISR is induced because unassembled eIF2B tetramer subcomplexes accumulate in cells. Upon addition of the small-molecule ISR inhibitor ISRIB, eIF2B tetramers assemble into active octamers. Surprisingly, ISRIB inhibits the ISR even in the context of fully assembled eIF2B decamers, revealing allosteric communication between the physically distant eIF2, eIF2-P, and ISRIB binding sites. Cryo-electron microscopy structures suggest a rocking motion in eIF2B that couples these binding sites. eIF2-P binding converts eIF2B decamers into 'conjoined tetramers' with diminished substrate binding and enzymatic activity. Canonical eIF2-P-driven ISR activation thus arises due to this change in eIF2B's conformational state.

PubMed: 33688831
DOI: 10.7554/eLife.65703

実験手法

ELECTRON MICROSCOPY (2.8 Å)