0382088 - ÚVGZ 2013 RIV US eng J - Journal Article
Nikouee, A. - Khabiri, Morteza - Grissmer, S. - Ettrich, Rüdiger
Charybdotoxin and Margatoxin Acting on the Human Voltage-Gated Potassium Channel hKv1.3 and Its H399N Mutant. An Experimental and Computational Comparison.
Journal of Physical Chemistry B. Roč. 116, č. 17 (2012), s. 5132-5140. ISSN 1520-6106. E-ISSN 1520-5207
Institutional support: RVO:67179843
Keywords : Charbydotoxin * dependent k + channel * constant-pressure * molecular dynamics simulations * scorpion toxin * force-field
Subject RIV: CE - Biochemistry
Impact factor: 3.607, year: 2012

The effect of the pore-blocking peptides charybdotoxin and margatoxin, both scorpion toxins, on currents through human voltage-gated hK(v)1.3 wild-type and hK(v)1.3_H399N mutant potassium channels was characterized by the whole-cell patch clamp technique. In the mutant channels, both toxins hardly blocked current through the channels, although they did prevent C-type inactivation by slowing down the current decay during depolarization. Molecular dynamics simulations suggested that the fast current decay in the mutant channel was a consequence of amino acid reorientations behind the selectivity filter and indicated that the rigidity-flexibility in that region played a key role in its interactions with scorpion toxins. A channel with a slightly more flexible selectivity filter region exhibits distinct interactions with scorpion toxins. Our studies suggest that the toxin-channel interactions might partially restore rigidity in the selectivity filter and thereby prevent the structural rearrangements associated with C-type inactivation.
Permanent Link: http://hdl.handle.net/11104/0007181