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Structural basis for the inhibition of translation through eIF2α phosphorylation

Author

Listed:
  • Yuliya Gordiyenko

    (MRC Laboratory of Molecular Biology)

  • José Luis Llácer

    (MRC Laboratory of Molecular Biology
    Instituto de Biomedicina de Valencia del Consejo Superior de Investigaciones Científicas and CIBERER-ISCIII)

  • V. Ramakrishnan

    (MRC Laboratory of Molecular Biology)

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.

Suggested Citation

  • Yuliya Gordiyenko & José Luis Llácer & V. Ramakrishnan, 2019. "Structural basis for the inhibition of translation through eIF2α phosphorylation," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10606-1
    DOI: 10.1038/s41467-019-10606-1
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    Cited by:

    1. Michael Schoof & Lan Wang & J. Zachery Cogan & Rosalie E. Lawrence & Morgane Boone & Jennifer Deborah Wuerth & Adam Frost & Peter Walter, 2021. "Viral evasion of the integrated stress response through antagonism of eIF2-P binding to eIF2B," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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