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-Structure paper
| タイトル | Termination of the integrated stress response. |
|---|---|
| ジャーナル・号・ページ | Science, Vol. 391, Issue 6787, Page eadw5137, Year 2026 |
| 掲載日 | 2026年2月19日 |
著者 | Claudia De Miguel / Sigurdur R Thorkelsson / Agnieszka Fatalska / George Hodgson / Maximillian Dalglish / Chao Wang / Anne Bertolotti / ![]() |
| PubMed 要旨 | Stress responses enable cells to detect, adapt to, and survive challenges. The benefit of these signaling pathways depends on their reversibility. The integrated stress response (ISR) is elicited by ...Stress responses enable cells to detect, adapt to, and survive challenges. The benefit of these signaling pathways depends on their reversibility. The integrated stress response (ISR) is elicited by phosphorylation of eukaryotic translation initiation factor eIF2, which traps and inhibits rate-limiting translation factor eIF2B, thereby attenuating translation initiation. Termination of this pathway thus requires relieving eIF2B from P-eIF2 inhibition. Here, we found that eIF2 phosphatase subunits PPP1R15A and PPP1R15B (R15B) bound P-eIF2 in complex with eIF2B. Biochemical investigations guided by cryo-electron microscopy structures of native eIF2-eIF2B and P-eIF2-eIF2B complexes bound to R15B demonstrated that R15B enabled dephosphorylation of otherwise dephosphorylation-incompetent P-eIF2 on eIF2B. This sheds light on ISR termination, revealing that R15B rescues eIF2B from P-eIF2 inhibition, thereby safeguarding translation and cell fitness. |
リンク | Science / PubMed:41231936 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.7 - 3.8 Å |
| 構造データ | EMDB-52432, PDB-9hvd: EMDB-52433, PDB-9hve: EMDB-52434, PDB-9hvf: |
| 化合物 | ![]() ChemComp-GTP: |
| 由来 |
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キーワード | TRANSLATION / phosphorylation / Eukaryotic Initiation Factor-2B / Eukaryotic Initiation Factor-2 / Translation Complex Catalytic Native |
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Expi293 cells (ヒト)
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