Structural basis for the inhibition of translation through eIF2α phosphorylation
Spheres representation of the eIF2B-eIF2 complex structure obtained by cryoEM, where 2 molecules of the eIF2 heterotrimer bind at opposite sides of the eIF2B heterodecamer. Phosphorylated eIF2alpha is trapped in between the alpha and delta subunits of eIF2B
Gordiyenko Y, Llacer JL, Ramakrishnan V.
Nat Commun 2019 Jun; 10: 2640.
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 A. Two eIF2 molecules bind opposite sides of an eIF2B hetero-decamer through eIF2alpha-D1, which contains the phosphorylated Ser51. eIF2alpha-D1 is mainly inserted between the N-terminal helix bundle domains of delta and alpha subunits of eIF2B. Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups with residues in eIF2Balpha and indirectly by inducing contacts of eIF2alpha helix 58-63 with eIF2Bdelta leading to a competition with Met-tRNAi.
PubMed: 31201334. Doi: 10.1038/s41467-019-10606-1. OPEN Free PMC
