ArticleThe Journal of biological chemistry2014
Crystal structures of GCN2 protein kinase C-terminal domains suggest regulatory differences in yeast and mammals.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Substrate Binding Relieves Autoinhibition of the Mammalian GCN2 Kinase.bioRxiv : the preprint server for biology · 2026Article
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- Structural basis for pseudokinase-mediated regulation of GCN2 in the integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structure of a Gcn2 dimer in complex with the large 60S ribosomal subunit.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The protein kinases family in fungi: adaptability, virulence and conservation between species.Frontiers in microbiology · 2025Review
- Purification and Analysis of eIF2α Phosphorylation by Stress-Activated Protein Kinase Gcn2 from S. cerevisiae.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Cryo-EM structure of histidyl-tRNA synthetase-like domain reveals activating crossed helices at the core of GCN2.PNAS nexus · 2024Article
- Gcn2 structurally mimics and functionally repurposes the HisRS enzyme for the integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- Differential requirements for P stalk components in activating yeast protein kinase Gcn2 by stalled ribosomes during stress.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Activation and execution of the hepatic integrated stress response by dietary essential amino acid deprivation is amino acid specific.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Review: Emerging roles of the signaling network of the protein kinase GCN2 in the plant stress response.Plant science : an international journal of experimental plant biology · 2022Review
- The PERK Inhibitor GSK2606414 Enhances Reovirus Infection in Head and Neck Squamous Cell Carcinoma via an ATF4-Dependent Mechanism.Molecular therapy oncolytics · 2020Article
- Towards a model of GCN2 activation.Biochemical Society transactions · 2019Review
- Activation of GCN2 by the ribosomal P-stalk.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- GCN2 phosphorylates HIV-1 integrase and decreases HIV-1 replication by limiting viral integration.Scientific reports · 2017Article
- EIF2AK4 mutation as "second hit" in hereditary pulmonary arterial hypertension.Respiratory research · 2016Article
- Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation.eLife · 2016Article
- Involvement of general control nonderepressible kinase 2 in cancer cell apoptosis by posttranslational mechanisms.Molecular biology of the cell · 2015Article
- Interaction between the tRNA-binding and C-terminal domains of Yeast Gcn2 regulates kinase activity in vivo.PLoS genetics · 2015Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
In response to amino acid starvation, GCN2 phosphorylation of eIF2 leads to repression of general translation and initiation of gene reprogramming that facilitates adaptation to nutrient stress. GCN2 is a multidomain protein with key regulatory domains that directly monitor uncharged tRNAs which accumulate during nutrient limitation, leading to activation of this eIF2 kinase and translational control. A critical feature of regulation of this stress response kinase is its C-terminal domain (CTD). Here, we present high resolution crystal structures of murine and yeast CTDs, which guide a functional analysis of the mammalian GCN2. Despite low sequence identity, both yeast and mammalian CTDs share a core subunit structure and an unusual interdigitated dimeric form, albeit with significant differences. Disruption of the dimeric form of murine CTD led to loss of translational control by GCN2, suggesting that dimerization is critical for function as is true for yeast GCN2. However, although both CTDs bind single- and double-stranded RNA, murine GCN2 does not appear to stably associate with the ribosome, whereas yeast GCN2 does. This finding suggests that there are key regulatory differences between yeast and mammalian CTDs, which is consistent with structural differences.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.