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TitleThe structural basis of translational control by eIF2 phosphorylation.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 2136, Year 2019
Publish dateMay 13, 2019
AuthorsTomas Adomavicius / Margherita Guaita / Yu Zhou / Martin D Jennings / Zakia Latif / Alan M Roseman / Graham D Pavitt /
PubMed AbstractProtein synthesis in eukaryotes is controlled by signals and stresses via a common pathway, called the integrated stress response (ISR). Phosphorylation of the translation initiation factor eIF2 ...Protein synthesis in eukaryotes is controlled by signals and stresses via a common pathway, called the integrated stress response (ISR). Phosphorylation of the translation initiation factor eIF2 alpha at a conserved serine residue mediates translational control at the ISR core. To provide insight into the mechanism of translational control we have determined the structures of eIF2 both in phosphorylated and unphosphorylated forms bound with its nucleotide exchange factor eIF2B by electron cryomicroscopy. The structures reveal that eIF2 undergoes large rearrangements to promote binding of eIF2α to the regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subunits. Only minor differences are observed between eIF2 and eIF2αP binding to eIF2B, suggesting that the higher affinity of eIF2αP for eIF2B drives translational control. We present a model for controlled nucleotide exchange and initiator tRNA binding to the eIF2/eIF2B complex.
External linksNat Commun / PubMed:31086188 / PubMed Central
MethodsEM (single particle)
Resolution3.93 - 4.61 Å
Structure data

4404

6i3m

EMDB-4404, PDB-6i3m:
eIF2B:eIF2 complex, phosphorylated on eIF2 alpha serine 52.
Method: EM (single particle) / Resolution: 3.93 Å

4428

6i7t

EMDB-4428, PDB-6i7t:
eIF2B:eIF2 complex
Method: EM (single particle) / Resolution: 4.61 Å

Source
  • Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (yeast)
  • saccharomyces cerevisiae s288c (yeast)
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsTRANSLATION / Translational control eIF2 phosphorylation Integrated stress response eIF2B TRANSLATION / Translational control eIF2 Integrated stress response eIF2B TRANSLATION

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