Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5.
Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5.
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DOI：
10.1016/j.jmb.2010.11.046
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发表时间：
2011-02-11
影响因子：
5.6
通讯作者：
Chazin WJ
中科院分区：
文献类型：
--
作者：
Chagot B;Chazin WJ
The function of the human voltage-gated sodium channel NaV1.5 is regulated in part by intracellular calcium signals. The ubiquitous calcium sensor protein calmodulin (CaM) is an important part of the complex calcium-sensing apparatus in NaV1.5. CaM interacts with an IQ motif in the large intracellular C-terminal domain of the channel. Using co-expression and co-purification, we have been able to isolate a CaM-IQ motif complex and to determine its high-resolution structure in absence of calcium using multi-dimensional solution NMR. Under these conditions, the NaV1.5 IQ motif interacts with the C-terminal domain (C-lobe) of CaM, with the N-terminal domain remaining free in solution. The structure reveals that the C-lobe adopts a semi-open conformation with the IQ motif bound in a narrow hydrophobic groove. Sequence similarities between voltage-gated sodium channels and voltage-gated calcium channels suggest that the structure of the CaM-NaV1.5 IQ motif complex can serve as a general model for the interaction between CaM and ion channels IQ motifs under conditions of low calcium. The structure also provides insight into the biochemical basis for disease-associated mutations that map to the IQ motif in NaV1.5.
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