CASK Functions as a Mg2+-Independent Neurexin Kinase

摘要: CASK is a unique MAGUK protein that contains an N-terminal CaM-kinase domain besides the typical domains. The presumed to be catalytically inactive pseudokinase because it lacks canonical DFG motif required for Mg2+ binding thought indispensable kinase activity. Here we show, however, functions as active even without binding. High-resolution crystal structures reveal adopts constitutively conformation binds ATP and catalyzes phosphotransfer Mg2+. phosphorylates itself at least one physiological interactor, synaptic neurexin-1, which recruited via its PDZ domain. Thus, our data indicate combines scaffolding activity of MAGUKs with unusual substrates recuited by Moreover, study suggests other pseudokinases (10% kinome) could also active.