Memory formation transpires to be by activation and persistent modification of synapses. A chain of biochemical events accompany synaptic activation and culminate in memory formation. These biochemical events are steered by interplay and modulation of various synaptic proteins, achieved by conformational changes and phosphorylation/dephosphorylation of these proteins. Calcium/calmodulin dependent protein kinase II (CaMKII) and N-methyl-d-aspartate receptors (NMDARs) are synaptic proteins whose interactions play a pivotal role in learning and memory process. Catalytic activity of CaMKII is modulated upon its interaction with the GluN2B subunit of NMDAR. The structural basis of this interaction is not clearly understood. We have investigated the role of Glu60 of α-CaMKII, a conserved residue present in the ATP binding region of kinases, in the regulation of catalysis of CaMKII by GluN2B. Mutation of Glu60 to Gly exerts different effects on the kinetic parameters of phosphorylation of GluN2B and GluN2A, of which only GluN2B binds to the T-site of CaMKII. GluN2B induced modulation of the kinetic parameters of peptide substrate was altered in the E60G mutant. The mutation almost abolished the modulation of the apparent Km value for protein substrate. However, although kinetic parameters for ATP were altered by mutating Glu60, modulation of the apparent Km value for ATP by GluN2B seen in WT was exhibited by the E60G mutant of α-CaMKII. Hence our results posit that the communication of the T-site of CaMKII with protein substrate binding region of active site is mediated through Glu60 while the communication of the T-site with the ATP binding region is not entirely dependent on Glu60.

中文翻译：

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α-钙/钙调蛋白依赖性蛋白激酶II的Glu60介导调节性T位点与活​​性位点的蛋白底物结合区之间的串扰。

记忆形成是通过激活和持续修饰突触而发生的。一连串的生化事件伴随着突触激活，并最终形成记忆。这些生化事件是通过各种突触蛋白的相互作用和调节来控制的，这些突触蛋白通过这些蛋白的构象变化和磷酸化/去磷酸化来实现。钙/钙调蛋白依赖性蛋白激酶II（CaMKII）和N-甲基-d-天冬氨酸受体（NMDARs）是突触蛋白，其相互作用在学习和记忆过程中起关键作用。CaMKII与NMDAR的GluN2B亚基相互作用时，其催化活性受到调节。这种相互作用的结构基础尚不清楚。我们研究了α-CaMKIIGlu60的作用，α-CaMKII是激酶的ATP结合区域中存在的保守残基，GluN2B调节CaMKII的催化作用 Glu60突变为Gly对GluN2B和GluN2A磷酸化动力学参数的作用不同，其中只有GluN2B结合到CaMKII的T位。在E60G突变体中，GluN2B诱导的对肽底物动力学参数的调节发生了改变。该突变几乎消除了蛋白质底物的表观Km值的调节。然而，尽管通过使Glu60突变而改变了ATP的动力学参数，但α-CaMKII的E60G突变体却显示出WT中GluN2B对ATP的表观Km值的调节。因此，我们的研究结果表明，CaMKII的T位点与活​​性位点的蛋白底物结合区的通讯是通过Glu60介导的，而T位点与ATP结合区的通讯并不完全依赖于Glu60。