Gcn2 structurally mimics and functionally repurposes the HisRS enzyme for the integrated stress response.

ABSTRACT: Protein kinase Gcn2 attenuates protein synthesis in response to amino acid starvation while stimulating translation of a transcriptional activator of amino acid biosynthesis. Gcn2 activation requires a domain related to histidyl-tRNA synthetase (HisRS), the enzyme that aminoacylates tRNA^His. While evidence suggests that deacylated tRNA binds the HisRS domain for kinase activation, ribosomal P-stalk proteins have been implicated as alternative activating ligands on stalled ribosomes. We report crystal structures of the HisRS domain of Chaetomium thermophilum Gcn2 that reveal structural mimicry of both catalytic (CD) and anticodon-binding (ABD) domains, which in authentic HisRS bind the acceptor stem and anticodon loop of tRNA^His. Elements for forming histidyl ad

SUBMITTER: Bou-Nader C 

PROVIDER: S-EPMC11363354 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature