7RLO

Structure of the human eukaryotic translation initiation factor 2B (eIF2B) in complex with a viral protein NSs

7RLO の概要

• エントリーDOI: 10.2210/pdb7rlo/pdb
• EMDBエントリー: 24535
• 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, ... (6 entities in total)
• 機能のキーワード: complex, viral protein, integrated stress response, protein translation, translation
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 583746.17

構造登録者

Wang, L.,Schoof, M.,Cogan, J.,Lawrence, R.,Boone, M.,Wuerth, J.,Frost, M.,Walter, P. (登録日: 2021-07-26, 公開日: 2021-12-22, 最終更新日: 2024-06-05)

主引用文献

Schoof, M.,Wang, L.,Cogan, J.Z.,Lawrence, R.E.,Boone, M.,Wuerth, J.D.,Frost, A.,Walter, P.
Viral evasion of the integrated stress response through antagonism of eIF2-P binding to eIF2B.
Nat Commun, 12:7103-7103, 2021

PubMed Abstract: Viral infection triggers activation of the integrated stress response (ISR). In response to viral double-stranded RNA (dsRNA), RNA-activated protein kinase (PKR) phosphorylates the translation initiation factor eIF2, converting it from a translation initiator into a potent translation inhibitor and this restricts the synthesis of viral proteins. Phosphorylated eIF2 (eIF2-P) inhibits translation by binding to eIF2's dedicated, heterodecameric nucleotide exchange factor eIF2B and conformationally inactivating it. We show that the NSs protein of Sandfly Fever Sicilian virus (SFSV) allows the virus to evade the ISR. Mechanistically, NSs tightly binds to eIF2B (K= 30 nM), blocks eIF2-P binding, and rescues eIF2B GEF activity. Cryo-EM structures demonstrate that SFSV NSs and eIF2-P directly compete, with the primary NSs contacts to eIF2Bα mediated by five 'aromatic fingers'. NSs binding preserves eIF2B activity by maintaining eIF2B's conformation in its active A-State.

PubMed: 34876554
DOI: 10.1038/s41467-021-26164-4

実験手法

ELECTRON MICROSCOPY (2.6 Å)