4OTN

Crystal structure of the C-terminal regulatory domain of murine GCN2

Summary for 4OTN

• Entry DOI: 10.2210/pdb4otn/pdb
• Related: 4OTM
• Descriptor: Eukaryotic translation initiation factor 2-alpha kinase 4, SULFATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: c-terminal regulatory domain, gcn2, 4-stranded beta sheet 3 helix bundle, regulatory domain of eif2 stress kinase, transferase
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm : Q9QZ05
• Total number of polymer chains: 2
• Total formula weight: 31996.50

Authors

He, H.,Georgiadis, M.M. (deposition date: 2014-02-13, release date: 2014-04-16, Last modification date: 2024-02-28)

Primary citation

He, H.,Singh, I.,Wek, S.A.,Dey, S.,Baird, T.D.,Wek, R.C.,Georgiadis, M.M.
Crystal Structures of GCN2 Protein Kinase C-terminal Domains Suggest Regulatory Differences in Yeast and Mammals.
J.Biol.Chem., 289:15023-15034, 2014

PubMed 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.

PubMed: 24719324
DOI: 10.1074/jbc.M114.560789

Experimental method

X-RAY DIFFRACTION (1.9 Å)