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DOI | 10.1126/science.aar5129 |
Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B | |
Zyryanova, Alisa F.1; Weis, Felix1,2,3,4; Faille, Alexandre1,2,3; Alard, Akeel Abo5; Crespillo-Casado, Ana1; Sekine, Yusuke1; Harding, Heather P.1; Allen, Felicity6; Parts, Leopold6; Fromont, Christophe5; Fischer, Peter M.5; Warren, Alan J.1,2,3,4; Ron, David1 | |
2018-03-30 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 359期号:6383页码:1533-1536 |
文章类型 | Article |
语种 | 英语 |
国家 | England |
英文摘要 | The integrated stress response (ISR) is a conserved translational and transcriptional program affecting metabolism, memory, and immunity. The ISR is mediated by stress-induced phosphorylation of eukaryotic translation initiation factor 2a (eIF2a) that attenuates the guanine nucleotide exchange factor eIF2B. A chemical inhibitor of the ISR, ISRIB, reverses the attenuation of eIF2B by phosphorylated eIF2a, protecting mice from neurodegeneration and traumatic brain injury. We describe a 4.1-angstrom-resolution cryo-electron microscopy structure of human eIF2B with an ISRIB molecule bound at the interface between the b and d regulatory subunits. Mutagenesis of residues lining this pocket altered the hierarchical cellular response to ISRIB analogs in vivo and ISRIB binding in vitro. Our findings point to a site in eIF2B that can be exploited by ISRIB to regulate translation. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000428657000048 |
WOS关键词 | PHOSPHORYLATION ; MUTATIONS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/198291 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England; 2.Univ Cambridge, Dept Haematol, Cambridge, England; 3.Univ Cambridge, Wellcome Trust Med Res Council Stem Cell Inst, Cambridge, England; 4.MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England; 5.Univ Nottingham, Sch Pharm, Div Biomol Sci & Med Chem, Nottingham NG7 2RD, England; 6.Wellcome Trust Sanger Inst, Wellcome Genome Campus, Hinxton CB10 1SA, Cambs, England |
推荐引用方式 GB/T 7714 | Zyryanova, Alisa F.,Weis, Felix,Faille, Alexandre,et al. Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B[J]. SCIENCE,2018,359(6383):1533-1536. |
APA | Zyryanova, Alisa F..,Weis, Felix.,Faille, Alexandre.,Alard, Akeel Abo.,Crespillo-Casado, Ana.,...&Ron, David.(2018).Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B.SCIENCE,359(6383),1533-1536. |
MLA | Zyryanova, Alisa F.,et al."Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B".SCIENCE 359.6383(2018):1533-1536. |
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