ARCHITECTURE OF THE BETA2/BETA4-NAV CHANNEL SIGNALING COMPLEX
Gilchrist, John Michael
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The voltage-gated sodium (Nav) channel complex is comprised of a channel-forming, ion-conducting alpha-subunit and one or multiple accessory beta-subunits. The latter has been shown to influence the function of Nav channels and mutations within the beta-subunit have been tied to cardiac and neurologic disorders. We show here that beta-subunits can also affect the pharmacology of Nav channels, particularly in relation to toxins derived from animal venoms. In this work we combine our knowledge of toxin binding sites with novel crystal structures of two beta-subunits to determine the cysteine residues responsible for forming the disulfide bridge between the beta2/beta4 subunits and the Nav1.2 channel. In doing so, we provide a basis for understanding the interaction between the beta-subunits and Nav channels and the functional consequences of this interaction.