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Domain II of the translation elongation factor eEF1A is required for Gcn2 kinase inhibition
Author(s) -
Ramesh Rashmi,
Sattlegger Evelyn
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13803
Subject(s) - elongation factor , translation (biology) , protein biosynthesis , eif2 , eukaryotic translation , biology , phosphorylation , microbiology and biotechnology , kinase , eukaryotic translation elongation factor 1 alpha 1 , eukaryotic initiation factor , biochemistry , ribosome , messenger rna , rna , gene
The signalling pathway governing general control nonderepressible (Gcn)2 kinase allows cells to cope with amino acid shortage. Under starvation, Gcn2 phosphorylates the translation initiation factor eukaryotic translation initiation factor (eIF)2α, triggering downstream events that ultimately allow cells to cope with starvation. Under nutrient‐replete conditions, the translation elongation factor eEF1A binds Gcn2 to contribute to keeping Gcn2 inactive. Here, we aimed to map the regions in eEF1A involved in binding and/or regulating Gcn2. We find that eEF1A amino acids 1–221 and 222–315, containing most of domains I and II, respectively, bind Gcn2 in vitro . Overexpression of eEF1A lacking or containing domain III impairs eIF2α phosphorylation. While the latter reduces growth under starvation similarly to eEF1A lacking domain I, the former enhances growth in a Gcn2‐dependent manner. Our studies suggest that domain II is required for Gcn2 inhibition and that eEF1A lacking domain III mainly affects the Gcn2 response pathway downstream of Gcn2.