3c0g
CASK CaM-Kinase Domain- 3'-AMP complex, P1 form
OverviewOverview
CASK is a unique MAGUK protein that contains an N-terminal CaM-kinase domain besides the typical MAGUK domains. The CASK CaM-kinase domain is presumed to be a catalytically inactive pseudokinase because it lacks the canonical DFG motif required for Mg2+ binding that is thought to be indispensable for kinase activity. Here we show, however, that CASK functions as an active protein kinase even without Mg2+ binding. High-resolution crystal structures reveal that the CASK CaM-kinase domain adopts a constitutively active conformation that binds ATP and catalyzes phosphotransfer without Mg2+. The CASK CaM-kinase domain phosphorylates itself and at least one physiological interactor, the synaptic protein neurexin-1, to which CASK is recruited via its PDZ domain. Thus, our data indicate that CASK combines the scaffolding activity of MAGUKs with an unusual kinase activity that phosphorylates substrates recuited by the scaffolding activity. Moreover, our study suggests that other pseudokinases (10% of the kinome) could also be catalytically active.
About this StructureAbout this Structure
3C0G is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
CASK Functions as a Mg2+-independent neurexin kinase., Mukherjee K, Sharma M, Urlaub H, Bourenkov GP, Jahn R, Sudhof TC, Wahl MC, Cell. 2008 Apr 18;133(2):328-39. PMID:18423203 Page seeded by OCA on Wed Apr 30 13:34:48 2008