4E53

Calmodulin and Nm peptide complex

Summary for 4E53

• Entry DOI: 10.2210/pdb4e53/pdb
• Related: 4E50
• Descriptor: Calmodulin, Linker, IQ motif of Neuromodulin (2 entities in total)
• Functional Keywords: calmodulin (cam), intrinsically unstructured proteins, protein kinase c (pkc), neuromodulin, growth associated protein -43 (gap-43), long term potentiation (ltp), long term depression (ltd), iq motif, protein binding
• Biological source: Mus musculus (mouse); More
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: P06837
• Total number of polymer chains: 2
• Total formula weight: 41486.13

Authors

Kumar, V.,Sivaraman, J. (deposition date: 2012-03-13, release date: 2013-03-20, Last modification date: 2024-03-20)

Primary citation

Kumar, V.,Chichili, V.P.R.,Zhong, L.,Tang, X.,Velazquez-Campoy, A.,Sheu, F.-S.,Seetharaman, J.,Gerges, N.Z.,Sivaraman, J.
Structural basis for the interaction of unstructured neuron specific substrates neuromodulin and neurogranin with calmodulin
Sci Rep, 3:1392-1392, 2013

PubMed 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.

PubMed: 23462742
DOI: 10.1038/srep01392

Experimental method

X-RAY DIFFRACTION (2.69 Å)