Research Article

Structural basis of α-scorpion toxin action on Nav channels

See allHide authors and affiliations

Science  22 Mar 2019:
Vol. 363, Issue 6433, eaav8573
DOI: 10.1126/science.aav8573

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

How activation leads to gating

Voltage-gated sodium (Nav) 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 NavPaS is replaced with VSD4 from human Nav1.7, 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

View Full Text