Solution NMR Structure of Apo-Calmodulin in Complex with the IQ Motif of Human Cardiac Sodium Channel NaV1.5 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Molecular Biology Année : 2011

Solution NMR Structure of Apo-Calmodulin in Complex with the IQ Motif of Human Cardiac Sodium Channel NaV1.5

Résumé

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.
Fichier principal
Vignette du fichier
nihms-259486.pdf (3.28 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01636790 , version 1 (01-12-2017)

Identifiants

Citer

Benjamin Chagot, Walter J. Chazin. Solution NMR Structure of Apo-Calmodulin in Complex with the IQ Motif of Human Cardiac Sodium Channel NaV1.5. Journal of Molecular Biology, 2011, 406 (1), pp.106 - 119. ⟨10.1016/j.jmb.2010.11.046⟩. ⟨hal-01636790⟩
20 Consultations
209 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More