Please use this identifier to cite or link to this item:
|Title:||Structural basis for the interaction of unstructured neuron specific substrates neuromodulin and neurogranin with calmodulin|
|Citation:||Kumar, V., Chichili, V.P.R., Zhong, L., Tang, X., Velazquez-Campoy, A., Sheu, F.-S., Seetharaman, J., Gerges, N.Z., Sivaraman, J. (2013). Structural basis for the interaction of unstructured neuron specific substrates neuromodulin and neurogranin with calmodulin. Scientific Reports 3 : -. ScholarBank@NUS Repository. https://doi.org/10.1038/srep01392|
|Abstract:||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.|
|Source Title:||Scientific Reports|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Mar 21, 2019
WEB OF SCIENCETM
checked on Mar 11, 2019
checked on Mar 8, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.