Abstract 2069 Insights Into Mechanisms of the Activation and Activity of Eukaryotic Elongation Factor-2 Kinase

In eukaryotes, the elongation factor-2 kinase (eEF2K) downregulates protein biosynthesis by phosphorylating residue T56 on the GTPase eEF2, putatively hindering its ability to engage the ribosome. eEF2K is a member of the atypical family of α-kinases whose activation, regulation, and catalytic mechanisms remain poorly understood. It is the only α-kinase that relies on calmodulin (CaM) for activation, which occurs through a unique mechanism distinct from other CaM-activated kinases. Upregulation of eEF2K activity involves binding calmodulin (CaM), autophosphorylation on a specific threonine residue (T348), and the intermolecular docking of this phospho-threonine into a conserved regulatory site.