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Nat Commun. 2019 Jun 14;10(1):2640. doi: 10.1038/s41467-019-10606-1.

Structural basis for the inhibition of translation through eIF2α phosphorylation.

Author information

1
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
2
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. jllacer@ibv.csic.es.
3
Instituto de Biomedicina de Valencia del Consejo Superior de Investigaciones Científicas and CIBERER-ISCIII, Valencia, 46010, Spain. jllacer@ibv.csic.es.

Abstract

One of the responses to stress by eukaryotic cells is the down-regulation of protein synthesis by phosphorylation of translation initiation factor eIF2. Phosphorylation results in low availability of the eIF2 ternary complex (eIF2-GTP-tRNAi) by affecting the interaction of eIF2 with its GTP-GDP exchange factor eIF2B. We have determined the cryo-EM structure of yeast eIF2B in complex with phosphorylated eIF2 at an overall resolution of 4.2 Å. Two eIF2 molecules bind opposite sides of an eIF2B hetero-decamer through eIF2α-D1, which contains the phosphorylated Ser51. eIF2α-D1 is mainly inserted between the N-terminal helix bundle domains of δ and α subunits of eIF2B. Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups with residues in eIF2Bα and indirectly by inducing contacts of eIF2α helix 58-63 with eIF2Bδ leading to a competition with Met-tRNAi.

PMID:
31201334
PMCID:
PMC6572841
DOI:
10.1038/s41467-019-10606-1
[Indexed for MEDLINE]
Free PMC Article

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