3C0H

CASK CaM-Kinase Domain- AMPPNP complex, P1 form

Summary for 3C0H

• Entry DOI: 10.2210/pdb3c0h/pdb
• Related: 3C0G 3C0I
• Descriptor: Peripheral plasma membrane protein CASK, ADENOSINE MONOPHOSPHATE (3 entities in total)
• Functional Keywords: cask, neurexin, ca2+/calmodulin dependent protein kinase, mg2+, synaptic plasticity, pseudokinase, maguk, membrane-associated guanylate kinase, atp-binding, calmodulin-binding, magnesium, metal-binding, nucleotide-binding, nucleus, serine/threonine-protein kinase, sh3 domain, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (By similarity): O14936
• Total number of polymer chains: 2
• Total formula weight: 79208.68

Authors

Wahl, M.C. (deposition date: 2008-01-20, release date: 2008-04-29, Last modification date: 2024-04-03)

Primary citation

Mukherjee, K.,Sharma, M.,Urlaub, H.,Bourenkov, G.P.,Jahn, R.,Sudhof, T.C.,Wahl, M.C.
CASK Functions as a Mg2+-independent neurexin kinase
Cell(Cambridge,Mass.), 133:328-339, 2008

PubMed Abstract: 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.

PubMed: 18423203
DOI: 10.1016/j.cell.2008.02.036

Experimental method

X-RAY DIFFRACTION (2.3 Å)