Ser500 phosphorylation acts as a conformational switch to prime eEF-2K for activation.

ABSTRACT: Eukaryotic elongation factor-2 kinase (eEF-2K), a member of the α-kinase family of atypical serine/threonine kinases, phosphorylates eEF-2 to slow ribosomal translocation and modulate translational elongation. eEF-2K activation requires Ca²⁺/calmodulin (CaM) and integrates upstream signals through specific sites within an intrinsically disordered regulatory loop (R-loop; ∼321-520) that links the α-kinase core to a C-terminal domain. Unlike canonical CaM-dependent kinases that are activated by displacement of an autoinhibitory segment that occludes the active site, eEF-2K is activated by CaM-driven stabilization of an active state; Ca²⁺/CaM engagement triggers rapid autophosphorylation at T348, which is essential for full activity. Phosphorylation on S500, by eEF-2K or

SUBMITTER: Bohanon AL 

PROVIDER: S-EPMC12834908 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature