Structural analysis of a Nav channel chimera bound to an α-scorpion toxin reveals that the toxin traps VSD4 in a deactivated state, suggesting a mechanism for fast inactivation.
Structural analysis of a Nav channel chimera reveals the mechanism by which VSD4 activation leads to fast inactivation, providing insights into electrical signaling.
How activation leads to gating Voltage-gated sodium (Na v ) channels are key players in electrical signaling. Central to their function is fast inactivation, and mutants that impede this cause conditions such as epilepsy and pain syndromes. The channels have four voltage-sensing domains (VSDs), with VSD4 playing an important role in fast inactivation. Clairfeuille et al. determined the structures of a chimera in which VSD4 of the cockroach channel Na v PaS is replaced with VSD4 from human Na v 1.7, both in the apo state and bound to a scorpion toxin that impedes fast activation (see the Perspective by Chowdhury and Chanda). The toxin traps VSD4 in a deactivated state. Comparison with the apo structure shows how interactions between VSD4 and the carboxyl-terminal region change as VSD4 activates and suggests how this would lead to fast inactivation. Science , this issue p. eaav8573 ; see also p. 1278
Clairfeuille et al. (Fri,) reported a other. α-scorpion toxin vs. Apo state was evaluated on Structural determination of VSD4 chimera. Structural analysis of a Nav channel chimera bound to an α-scorpion toxin reveals that the toxin traps VSD4 in a deactivated state, suggesting a mechanism for fast inactivation.