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TitleStructural basis for the inhibition of translation through eIF2α phosphorylation.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 2640, Year 2019
Publish dateJun 14, 2019
AuthorsYuliya Gordiyenko / José Luis Llácer / V Ramakrishnan /
PubMed AbstractOne 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 ...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-tRNA.
External linksNat Commun / PubMed:31201334 / PubMed Central
MethodsEM (single particle)
Resolution4.15 - 10.4 Å
Structure data

4543

6qg0

EMDB-4543: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (map 1)
PDB-6qg0: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (model 1)
Method: EM (single particle) / Resolution: 4.15 Å

4544

6qg1

EMDB-4544: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (map 2)
PDB-6qg1: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (model 2)
Method: EM (single particle) / Resolution: 4.25 Å

4545

6qg2

EMDB-4545: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (map A)
PDB-6qg2: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (model A)
Method: EM (single particle) / Resolution: 4.55 Å

4546

6qg3

EMDB-4546: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (map B)
PDB-6qg3: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (model B)
Method: EM (single particle) / Resolution: 9.4 Å

4547

6qg5

EMDB-4547: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (map C)
PDB-6qg5: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (model C)
Method: EM (single particle) / Resolution: 10.1 Å

4548

6qg6

EMDB-4548: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (map D)
PDB-6qg6: Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (model D)
Method: EM (single particle) / Resolution: 10.4 Å

Source
  • Saccharomyces cerevisiae S288C (yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsTRANSLATION / integrated stress response / ISR / initiation factors / phosphorylation / eIF2 / eIF2B / tRNAi / GEF / heat domain / eIF2 alpha

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