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

We describe a 4.1-angstrom-resolution cryo–electron microscopy structure of human eIF2B with an ISRIB molecule bound at the interface between the β and 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.

Source: ScienceNOW - March 29, 2018 Category: Science Authors: Zyryanova, A. F., Weis, F., Faille, A., Alard, A. A., Crespillo-Casado, A., Sekine, Y., Harding, H. P., Allen, F., Parts, L., Fromont, C., Fischer, P. M., Warren, A. J., Ron, D. Tags: Biochemistry, Cell Biology reports Source Type: news