| First Author | Kumar V | Year | 2013 |
| Journal | Sci Rep | Volume | 3 |
| Pages | 1392 | PubMed ID | 23462742 |
| Mgi Jnum | J:344998 | Mgi Id | MGI:6218339 |
| Doi | 10.1038/srep01392 | Citation | Kumar V, et al. (2013) Structural basis for the interaction of unstructured neuron specific substrates neuromodulin and neurogranin with Calmodulin. Sci Rep 3:1392 |
| abstractText | 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. |
