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Phosphorylation of translation initiation factor eIF2? at Ser51 depends on site- and context-specific information.

ABSTRACT: Protein kinases phosphorylate specific amino acid residues of substrate proteins and regulate many cellular processes. Specificity for phosphorylation depends on the accessibility of these residues, and more importantly, kinases have preferences for certain residues flanking the phospho-acceptor site. Translation initiation factor 2? [eukaryotic translation initiation factor 2? (eIF2?)] kinase phosphorylates serine51 (Ser51) of eIF2? and downregulates cellular protein synthesis. Structural information on eIF2? reveals that Ser51 is located within a flexible loop, referred to as the Ser51 loop. Recently, we have shown that conformational change of the Ser51 loop increases the accessibility of Ser51 to the kinase active site for phosphorylation. Here, we show that the specificity of Ser51 phosphorylation depends largely on its relative position in the Ser51 loop and minimally on the flanking residues.

SUBMITTER: Uppala JK

PROVIDER: S-EPMC6167009 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Phosphorylation of translation initiation factor eIF2α at Ser51 depends on site- and context-specific information.

Uppala Jagadeesh Kumar JK Ghosh Chandrima C Sathe Leena L Dey Madhusudan M

FEBS letters 20180919 18

Protein kinases phosphorylate specific amino acid residues of substrate proteins and regulate many cellular processes. Specificity for phosphorylation depends on the accessibility of these residues, and more importantly, kinases have preferences for certain residues flanking the phospho-acceptor site. Translation initiation factor 2α [eukaryotic translation initiation factor 2α (eIF2α)] kinase phosphorylates serine51 (Ser51) of eIF2α and downregulates cellular protein synthesis. Structural infor ...[more]

PMID: 30070006

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