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Structural basis for the inhibition of translation through eIF2? phosphorylation.

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 eIF2?-D1, which contains the phosphorylated Ser51. eIF2?-D1 is mainly inserted between the N-terminal helix bundle domains of ? and ? subunits of eIF2B. Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups with residues in eIF2B? and indirectly by inducing contacts of eIF2? helix 58-63 with eIF2B? leading to a competition with Met-tRNAi.

SUBMITTER: Gordiyenko Y

PROVIDER: S-EPMC6572841 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Structural basis for the inhibition of translation through eIF2α phosphorylation.

Gordiyenko Yuliya Y Llácer José Luis JL Ramakrishnan V V

Nature communications 20190614 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 het ...[more]

PMID: 31201334

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