Interaction between the tRNA-Binding and C-Terminal Domains of Yeast Gcn2 Regulates Kinase Activity In Vivo

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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 modulate general and gene-specific protein synthesis by phosphorylating the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). The yeast Saccharomyces cerevisiae has a single eIF2α kinase, Gcn2, activated by uncharged tRNAs that accumulate in amino acid starved cells, which bind to a regulatory domain homologous to histidyl-tRNA synthetase (HisRS). Gcn2 also contains a C-terminal domain implicated in autoinhibition of Gcn2. Our findings identify a direct interaction between the CTD and a novel regulatory surface in the HisRS domain that is required for inhibition of Gcn2 function in non-starved cells, which is down-regulated by uncharged tRNA. The results further suggest that tRNA binding to the pseudo-active site in the HisRS domain remodels its proximal CTD-binding surface to weaken HisRS/CTD interaction and thereby release the autoinhibitory function of the CTD to activate kinase function. This study provides new molecular insights into how tRNA binding can modulate regulatory interactions among the HisRS, CTD, and kinase domains of Gcn2 to elicit kinase activation.

Vyšlo v časopise: Interaction between the tRNA-Binding and C-Terminal Domains of Yeast Gcn2 Regulates Kinase Activity In Vivo. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004991
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004991

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