Abstract
Voltage-dependent or voltage-gated sodium channels (VDSC, VGSC, NaV1.x) control essential processes in muscle cells and neurons. Associated channelopathies include Dravet syndrome, epilepsy, Long QT syndrome 3, ventricular fibrillation, familial autism, pain insensitivity, and defects in the generation and propagation of action potentials. Calmodulin (CaM), a eukaryotic calcium sensor, regulates sodium channels by binding to the intracellular C-terminal region of the pore-forming alpha subunit. Thermodynamic analysis and high resolution structural (NMR) studies focusing on how apo (calcium-depleted) and calcium-saturated 13C-15N-CaM recognize an IQ-motif (IQxxxBGxxxB, B=K,R) located in the tail of NaV1.2 will be presented. These will be compared to studies of how CaM recognizes other sodium channels, unconventional myosin V (2IX7.pdb), and the small conductance potassium channel (1G4Y.pdb). NIH R01 GM57001.
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