2015年2月19日 · 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.

2024年6月6日 · GCN2 is a stress response kinase that phosphorylates the translation initiation factor eIF2α to inhibit general protein synthesis when activated by uncharged tRNA and stalled ribosomes. The presence of a HisRS-like domain in GCN2, normally associated with tRNA aminoacylation, led to the hypothesis t …

2024年6月6日 · The presence of a HisRS-like domain in GCN2, normally associated with tRNA aminoacylation, led to the hypothesis that eIF2α kinase activity is regulated by the direct binding of this domain to uncharged tRNA. Here we solved the structure of the HisRS-like domain in the context of full-length GCN2 by cryoEM.

GCN2 is capable of distinguishing between aminoacylated and deacylated tRNA species, and interactions between yeast GCN2 and deacylated tRNA have been demonstrated by both gel shift analysis and Northwestern assay and they are dependent on …

General control nonderepressible 2 (GCN2), which is encoded by eukaryotic translation initiation factor 2 alpha (eIF-2α) kinase 4 (EIF2AK4), is a serine/threonine-protein kinase that senses amino acid deficiencies through binding to uncharged transfer RNA (tRNA).

Overview of GCN2 protein domains and factors that activate GCN2. Active GCN2 phosphorylates the α subunit of eukaryotic translation initiation factor 2 which reduces global protein translation and induces selective stress-adaptive gene transcription, with targets including ATF4.

2023年4月1日 · For recognition of these diverse stresses, Gcn2 has an amino-terminal RWD-protein interaction domain, pseudo kinase and protein kinase domains, a region related to the histidyl tRNA synthetase (HARS), and a carboxy-terminal domain (CTD) that forms an interdigitated dimer and is suggested to facilitate Gcn2 binding to ribosomes (7, 8, 9) (Fig. 1A).

2024年11月21日 · The molecular mechanism of GCN2 switching is not well understood due to the presence of a structurally and biochemically uncharacterized histidyl-tRNA synthetase-like domain (HRSL) at the core of GCN2. Here, we use single-particle cryo-EM and biochemistry to elucidate the structure and function of HRSL.

2024年8月20日 · 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.

2018年2月14日 · GCN2, one of four known sensors of the ISR, can be activated by single amino acid deprivation. In the context of low levels of an amino acid, uncharged tRNA molecules accumulate and bind to the...