4E53

Calmodulin and Nm peptide complex

4E53 の概要

• エントリーDOI: 10.2210/pdb4e53/pdb
• 関連するPDBエントリー: 4E50
• 分子名称: Calmodulin, Linker, IQ motif of Neuromodulin (2 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cell membrane; Peripheral membrane protein; Cytoplasmic side: P06837
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41486.13

構造登録者

Kumar, V.,Sivaraman, J. (登録日: 2012-03-13, 公開日: 2013-03-20, 最終更新日: 2024-03-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.69 Å)