title: Calcium/calmodulin dependent protein kinase II bound to NMDA receptor 2B subunit exhibits increased ATP affinity and attenuated dephosphorylation.
abstract: Calcium/calmodulin dependent protein kinase II (CaMKII) is implicated to play a key role in learning and memory. NR2B subunit of N-methyl-D-aspartate receptor (NMDAR) is a high affinity binding partner of CaMKII at the postsynaptic membrane. NR2B binds to the T-site of CaMKII and modulates its catalysis. By direct measurement using isothermal titration calorimetry (ITC), we show that NR2B binding causes about 11 fold increase in the affinity of CaMKII for ATPγS, an analogue of ATP. ITC data is also consistent with an ordered binding mechanism for CaMKII with ATP binding the catalytic site first followed by peptide substrate. We also show that dephosphorylation of phospho-Thr(286)-α-CaMKII is attenuated when NR2B is bound to CaMKII. This favors the persistence of Thr(286) autophosphorylated state of CaMKII in a CaMKII/phosphatase conjugate system in vitro. Overall our data indicate that the NR2B- bound state of CaMKII attains unique biochemical properties which could help in the efficient functioning of the proposed molecular switch supporting synaptic memory.
authors.affiliation: Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: John
authors.initials: J
authors.lastname: Cheriyan
authors.forename: Parimal
authors.initials: P
authors.lastname: Kumar
authors.forename: Madhavan
authors.initials: M
authors.lastname: Mayadevi
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
authors.forename: Ramakrishnapillai V
authors.initials: RV
authors.lastname: Omkumar
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002151:Calorimetry; D007700:Kinetics; D008954:Models, Biological; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: C121001:NR2B NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D010769:Phosphothreonine; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2