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The structural basis of translational control by eIF2 phosphorylation.

ABSTRACT: 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 eIF2? to the regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subunits. Only minor differences are observed between eIF2 and eIF2?P binding to eIF2B, suggesting that the higher affinity of eIF2?P for eIF2B drives translational control. We present a model for controlled nucleotide exchange and initiator tRNA binding to the eIF2/eIF2B complex.

SUBMITTER: Adomavicius T

PROVIDER: S-EPMC6513899 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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The structural basis of translational control by eIF2 phosphorylation.

Adomavicius Tomas T Guaita Margherita M Zhou Yu Y Jennings Martin D MD Latif Zakia Z Roseman Alan M AM Pavitt Graham D GD

Nature communications 20190513 1

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 cryomi ...[more]

PMID: 31086188

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