title: Transfer of the scorpion toxin receptor to an insensitive potassium channel.
abstract: Voltage-dependent potassium channels belong to a family of structurally related cation channels that underlie the electrical activity of excitable cells. Many potassium channels are blocked with high affinity by scorpion toxins, whereas others are completely insensitive. We transferred toxin sensitivity from the highly sensitive Kv1.3 (KV3) to the insensitive Kv2.1 (DRK1) potassium channel by transferring the stretch of amino acids between transmembrane domains 5/6. We provide evidence that this S5-S6 linker, which has been shown to comprise the pore-forming region, is probably the only part of the ion channel that directly interacts with bound toxin. Using site-directed mutagenesis, we identified specific residues in the S5-S6 linker that are responsible for the acquisition of toxin sensitivity by Kv2.1.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: A
authors.initials: A
authors.lastname: Gross
authors.forename: T
authors.initials: T
authors.lastname: Abramson
authors.forename: R
authors.initials: R
authors.lastname: MacKinnon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D017385:Sequence Homology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014981:Xenopus
chemical_list: D015221:Potassium Channels; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D015222:Sodium Channels; C029574:scorpion toxin receptor