Enhanced Interaction between Pseudokinase and Kinase Domains in Gcn2 stimulates eIF2α Phosphorylation in Starved Cells

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The survival of all living organisms depends on their capacity to adapt their gene expression program to variations in the environment. When subjected to various stresses, eukaryotic cells down-regulate general protein synthesis by phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). The yeast Saccharomyces cerevisiae has a single eIF2α kinase, Gcn2, activated by uncharged tRNAs accumulating in amino acid starved cells, which bind to a regulatory domain homologous to histidyl-tRNA synthetase. Gcn2 also contains a degenerate, pseudokinase domain (YKD) of largely unknown function, juxtaposed to the authentic, functional kinase domain (KD). Our study demonstrates that direct interaction between the YKD and KD is essential for activation of Gcn2, and identifies likely KD-contact sites in the YKD that can be altered to either impair or constitutively activate kinase function. Our results provide the first functional insights into the regulatory role of the enigmatic YKD of Gcn2.

Vyšlo v časopise: Enhanced Interaction between Pseudokinase and Kinase Domains in Gcn2 stimulates eIF2α Phosphorylation in Starved Cells. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004326
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004326

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