Abstract 1972 Leveraging Calmodulin's C-lobe to Design a Constitutively Active Elongation Factor-2 Kinase

Eukaryotic elongation factor-2 kinase (eEF-2K) modulates elongation rates by phosphorylating translation factor eEF2, a GTPase that provides the energy for the translocation of ribosomes along mRNA. eEF-2K is regulated by diverse cellular cues, many of which sensitize it to the calcium-effector protein calmodulin (CaM), which binds and allosterically activates it in the presence of calcium. In the active complex, the C-terminal lobe (C-lobe) of CaM makes critical interactions with eEF-2K at the CaM targeting motif (CTM) and the kinase domain.