Key result
Structural determination of Nav1.7 and Nav1.2 channels in complex with auxiliary subunits and animal toxins provides a framework for targeted drug development.
Why the study?
Voltage-gated sodium channels are implicated in cardiac and neurological disorders, but multiple subtypes make developing specific therapeutics challenging.
The structural determination of Nav1.7 and Nav1.2 complexes provides a framework for targeted drug development for cardiac and neurological disorders.
Answers are grounded in this paper and cite their sources.
Nav channel structures may inform selective modulator design; leaves open clinical translation for cardiac disorders.
Targeting sodium channels Voltage-gated sodium (Na v ) channels have been implicated in cardiac and neurological disorders. There are many subtypes of these channels, making it challenging to develop specific therapeutics. A core α subunit is sufficient for voltage sensing and ion conductance, but function is modulated by β subunits and by natural toxins that can either act as pore blockers or gating modifiers (see the Perspective by Chowdhury and Chanda). Shen et al. present the structures of Na v 1.7 in complex with both β1 and β2 subunits and with animal toxins. Pan et al. present the structure of Na v 1.2 bound to β2 and a toxic peptide, the µ-conotoxin KIIIA. The structure shows why KIIIA is specific for Na v 1.2. These and other recently determined Na v structures provide a framework for targeted drug development. Science , this issue p. 1303 , p. 1309 ; see also p. 1278
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Shen et al. (2019) studied Cardiac and neurological disorders. Structural determination of Nav1.7 and Nav1.2 channels in complex with auxiliary subunits and animal toxins provides a framework for targeted drug development.
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