期刊
BIOCHEMICAL JOURNAL
卷 419, 期 -, 页码 123-132出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20081707
关键词
allosteric modulation; Ca2+/calmodulin-dependent protein kinase II (CaMKII); N-methyl-D-aspartate receptor (NMDAR); NR2B; phosphorylation
资金
- Rajiv Gandhi Centre for Biotechnology. Department at Science and Technology, Government of India
- Council of Scientific and Industrial Research, Government of India
- Council of Scientific and Industrial Research of the Government of India
Binding of CaMKII (Ca2+/calmodulin-dependent kinase 11) to the NR2B subunit of the NMDAR (N-methyl-D-aspartate-type glutamate receptor) in the PSD (postsynaptic density) is essential for the induction of long-term potentiation. In this study, we show that binding of NR2B to the T-site (Thr(286)-autophosphorylation site binding pocket) of CaMKII regulates its catalysis its reflected in the kinetic parameters. The apparent S-0.5 (Substrate concentration at half maximal velocity) and V-max Values for ATP were lower for phosphorylation of a GST (glutathione transferase)-fusion of NR2B(01271) (1310) (with the phosphorylation site Ser(1303)) when compared with phosphorylation of the analogous sequence rnotif from NR2A. The co-operative behaviour exhibited by the CaMKII holoenzyme towards ATP for phosphorylation of GST NR2A was significantly altered by the interaction with GST-NR2B. Disrupting the T-site-mediated binding by mutagenesis of either NR2B or CaMKII abolished the modulation of CaMKII activity by NR2B. The active site residue of alpha-CaMKII, Glu(96), participates in effecting the modulation. The CaMKII-binding motif of the Drosophila voltage-gated potassium channel Eag interacted with the T-site of CaMKII with lower affinity and caused catalytic modulation to a lesser extent. The kinetic parameters of ATP for the Thr(286)-autophosphorylation reaction of CaMKII were also altered by NR2B in a similar manner. Interestingly, the NR2B sequence motif caused increased sensitivity of CaMKII activity to ATP, and saturation by lower concentrations of ATP, which, in effect, resulted in a constant level of activity of CaMKII over a broad range of ATP concentrations. Our findings indicate that CaMKII at the PSD may be regulated by bound NR2B in I manner that Supports synaptic memories.
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