4OTM: Crystal structure of the C-terminal domain from yeast GCN2

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.
PDB ID: 4OTMDownload
MMDB ID: 119251
PDB Deposition Date: 2014/2/13
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 4OTM: dimeric; determined by author and by software (PISA)
Molecular Components in 4OTM
Label Count Molecule
Proteins (2 molecules)
Serine/threonine-protein Kinase Gcn2(Gene symbol: GCN2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB