The S631A mutation causes a mechanistic switch in the block of hERG channels by CnErg1 |
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Authors: | Hill Adam P Campbell T J Bansal P S Kuchel P W Vandenberg J I |
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Affiliation: | Victor Chang Cardiac Research Institute, New South Wales, Australia. |
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Abstract: | We have studied the interaction of CnErg1, a member of the gamma-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 gamma-KTXs on Kv11-type channels, to pore plugging, characteristic of alpha-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. |
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