Separate parts of GCN1 needed to bind GCN2 and ribosomes for activating GCN2 when cells lack amino acids

GCN2 binding to the C-terminal domain of GCN1, dependent on Arg2259, is required for high level GCN2 function in vivo.

• GCN2 stimulates translation of GCN4 in cells lacking amino acids by modifying a translation initiation factor.
• The GCN1/GCN20 complex is necessary for GCN2 function in living organisms.
• A specific segment of GCN1 is both necessary and sufficient for binding to GCN2.
• Overexpression of this GCN1 segment disrupts GCN2's association with native GCN1, leading to a dominant negative effect.
• Changes to a specific amino acid in GCN1 eliminate its ability to form a complex with GCN2 and regulate its function.
• GCN1's role in enhancing sensitivity to paromomycin is linked to its interaction with ribosomes.

Simplified