Solution NMR Structure of apo-calmodulin in complex with the IQ motif of Human Cardiac Sodium Channel Na(V)1.5.
 

Solution NMR Structure of apo-calmodulin in complex with the IQ motif of Human Cardiac Sodium Channel Na(V)1.5.

Solution NMR Structure of apo-calmodulin in complex with the IQ motif of Human Cardiac Sodium Channel Na(V)1.5.

J Mol Biol. 2010 Dec 14;

Authors: Chagot B, Chazin WJ

The function of the human voltage-gated sodium channel Na(V)1.5 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 Na(V)1.5. 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 Na(V)1.5 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-Na(V)1.5 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 Na(V)1.5.

PMID: 21167176 [PubMed - as supplied by publisher]



Source: PubMed