The S631A Mutation Causes a Mechanistic Switch in the Block of hERG Channels by CnErg1

Abstract

We have studied the interaction of CnErg1, a member of the γ-KTX subfamily of scorpion toxins with the inactivation-deficient S631A hERG channel. In the background of this mutation, we observed a mechanistic switch from turret block, characteristic of the action of γ-KTXs on Kv11-type channels, to pore plugging, characteristic of α-KTX block of Kv1-type channels. We suggest this reflects destabilization of the outer pore (turret region) of hERG allowing access of the toxin molecule to directly plug the conduction pathway.