Structural Basis for the Interaction of Unstructured Neuron Specific Substrates Neuromodulin and Neurogranin with Calmodulin

被引：55

作者：

Kumar, Veerendra ^{[1
]}

Chichili, Vishnu Priyanka Reddy ^{[1
]}

Zhong, Ling ^{[4
]}

Tang, Xuhua ^{[1
]}

Velazquez-Campoy, Adrian ^{[5
,6
]}

Sheu, Fwu-Shan ^{[2
]}

Seetharaman, J. ^{[3
]}

Gerges, Nashaat Z. ^{[4
]}

Sivaraman, J. ^{[1
]}

机构：

[1] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore

[2] Natl Univ Singapore, NUSNNI NanoCore, Singapore 117580, Singapore

[3] Brookhaven Natl Lab, Upton, NY 11973 USA

[4] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA

[5] Univ Zaragoza, Dept Biochem & Mol & Cell Biol, Inst Biocomputat & Phys Complex Syst BIFI, Unidad Asociada IQFR CSIC BIFI, E-50009 Zaragoza, Spain

[6] Diputac Gen Aragon, Fdn ARAID, Zaragoza, Spain

来源：

SCIENTIFIC REPORTS | 2013年 / 3卷

关键词：

KINASE-C SUBSTRATE; BINDING-PROTEIN; DOMAIN; EXPRESSION; GAP-43; TERM; CALCIUM/CALMODULIN; INVOLVEMENT; PROTEOMICS; REVEALS;

D O I：

10.1038/srep01392

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9