Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B-Reference-Cited by-同舟云学术

Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B

Published:2018-03-30 Issue:6383 Volume:359 Page:1533-1536
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Zyryanova Alisa F.¹^ORCID,Weis Félix¹²³⁴^ORCID,Faille Alexandre¹²³,Alard Akeel Abo⁵^ORCID,Crespillo-Casado Ana¹^ORCID,Sekine Yusuke¹,Harding Heather P.¹^ORCID,Allen Felicity⁶^ORCID,Parts Leopold⁶,Fromont Christophe⁵^ORCID,Fischer Peter M.⁵^ORCID,Warren Alan J.¹²³⁴^ORCID,Ron David¹^ORCID

Affiliation:

1. Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.

2. Department of Haematology, University of Cambridge, Cambridge, UK.

3. Wellcome Trust–Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.

4. MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.

5. Division of Biomolecular Science and Medicinal Chemistry, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.

6. Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.

Abstract

ISRIB mechanism of action In rodents, a druglike small molecule named ISRIB enhances cognition and reverses cognitive deficits after traumatic brain injury. ISRIB activates a protein complex called eIF2B that is required for the synthesis of new proteins. Tsai et al. report the visualization of eIF2B bound to ISRIB at near-atomic resolution by cryo–electron microscopy. Biochemical studies revealed that ISRIB is a “molecular staple” that promotes assembly of the fully active form of eIF2B. Zyryanova et al. report similar structures together with information on the binding of ISRIB analogs and their effects on protein translation. Science , this issue p. eaaq0939 , p. 1533

Funder

Wellcome Trust

Medical Research Council

Bloodwise

The Higher Committee for Education Development, Iraq

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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