Structural features of ZAK kinase regulation at the ribosome

ZAKα is a MAP3K that interacts with ribosomes and autophosphorylates upon widespread ribosome collisions mediating the ribotoxic stress response pathway. While activation of ZAKα determines downstream cell fate outcomes such as cell cycle arrest and apoptosis, the exact nature of ribosome binding and the mechanism of activation have not been fully understood. Our recent cryo‐EM structures contribute to bridging this gap by visualizing ZAKα bound to ribosomes in various states (hibernating, translating, and colliding) providing a clear molecular blueprint for ZAKα kinase regulation at the ribosome.