Structural basis for the inhibition of translation through eIF2α phosphorylation

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factor-2 / ultrastructure*
  • Eukaryotic Initiation Factor-2B / metabolism
  • Eukaryotic Initiation Factor-2B / ultrastructure*
  • Guanosine Diphosphate / metabolism
  • Models, Molecular
  • Phosphorylation / physiology
  • Protein Binding / physiology
  • Protein Biosynthesis / physiology*
  • RNA, Transfer, Met / metabolism
  • RNA, Transfer, Met / ultrastructure
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / ultrastructure*
  • Serine / metabolism


  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-2B
  • RNA, Transfer, Met
  • Saccharomyces cerevisiae Proteins
  • Guanosine Diphosphate
  • Serine