Structural basis for the interaction of unstructured neuron specific substrates neuromodulin and neurogranin with Calmodulin.
Structural basis for the interaction of unstructured neuron specific substrates neuromodulin and neurogranin with Calmodulin.
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DOI：
10.1038/srep01392
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发表时间：
2013
影响因子：
4.6
通讯作者：
Sivaraman, J.
中科院分区：
文献类型：
--
作者：
Kumar, Veerendra;Chichili, Vishnu Priyanka Reddy;Zhong, Ling;Tang, Xuhua;Velazquez-Campoy, Adrian;Sheu, Fwu-Shan;Seetharaman, J.;Gerges, Nashaat Z.;Sivaraman, J.
神经调节素（Nm）和神经颗粒素（Ng）是蛋白激酶C（PKC）的神经元特异性底物。它们与钙调素（CaM）的相互作用对神经元的学习和记忆形成至关重要。在这里，我们报告的IQ肽（24 aa）的Nm/Ng与钙调素复合物的结构和全长蛋白质的功能研究。Nm/Ng和它们各自的IQ肽本质上是非结构化的;然而，在与CaM结合时，IQ基序采用螺旋构象。Nm（Ng）的Ser 41（Ser 36）位于载脂蛋白CaM中的带负电荷的口袋中，并且当磷酸化时，它将从CaM排斥Nm/Ng。这些观察结果解释了PKC诱导的Ser磷酸化阻断Nm/Ng与CaM的关联并中断几种学习和记忆相关功能的机制。此外，本研究确定Arg作为Nm/Ng的关键CaM相互作用残基。该残基对于钙调素介导的功能是至关重要的，如Ng突变体（Arg-至-Ala）不能增强CA 1海马神经元中的突触传递所证明的。
Neuromodulin (Nm) and neurogranin (Ng) are neuron-specific substrates of protein kinase C (PKC). Their interactions with Calmodulin (CaM) are crucial for learning and memory formation in neurons. Here, we report the structure of IQ peptides (24aa) of Nm/Ng complexed with CaM and their functional studies with full-length proteins. Nm/Ng and their respective IQ peptides are intrinsically unstructured; however, upon binding with CaM, IQ motifs adopt a helical conformation. Ser41 (Ser36) of Nm (Ng) is located in a negatively charged pocket in the apo CaM and, when phosphorylated, it will repel Nm/Ng from CaM. These observations explain the mechanism by which PKC-induced Ser phosphorylation blocks the association of Nm/Ng with CaM and interrupts several learning- and memory-associated functions. Moreover, the present study identified Arg as a key CaM interacting residue from Nm/Ng. This residue is crucial for CaM-mediated function, as evidenced by the inability of the Ng mutant (Arg-to-Ala) to potentiate synaptic transmission in CA1 hippocampal neurons.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Kleerekoper, Quinn K.;Putkey, John A.
通讯作者：
Putkey, John A.
影响因子：
3
作者：
Clayton DF;George JM;Mello CV;Siepka SM
通讯作者：
Siepka SM
影响因子：
4.1
作者：
LEMAIRE, M;GHAZI, A;AGGERBECK, LP
通讯作者：
AGGERBECK, LP
影响因子：
11.4
作者：
HENDRICKSON, WA;HORTON, JR;LEMASTER, DM
通讯作者：
LEMASTER, DM