title: Charybdotoxin and margatoxin acting on the human voltage-gated potassium channel hKv1.3 and its H399N mutant: an experimental and computational comparison.
abstract: 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.
authors.affiliation: Institute of Applied Physiology, Ulm University, Ulm, Germany.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Nikouee
authors.forename: Morteza
authors.initials: M
authors.lastname: Khabiri
authors.forename: Stephan
authors.initials: S
authors.lastname: Grissmer
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Ettrich
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D018999:Charybdotoxin / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012604:Scorpion Venoms / Q000378:metabolism
chemical_list: D051664:Kv1.3 Potassium Channel; D012604:Scorpion Venoms; D018999:Charybdotoxin; C077910:margatoxin