Structural basis for pseudokinase-mediated regulation of GCN2 in the integrated stress response

Proceedings of the National Academy of Sciences, Volume 123, Issue 5, February 2026. <br/>SignificanceGCN2 is a multidomain effector of the integrated stress response, regulating protein synthesis under stress through phosphorylation of eIF2α. GCN2 contains a tandem kinase and pseudokinase domain (ψKD). Although the ψKD is essential for GCN2 …