Photoaffinity labeling of the receptor site for alpha-scorpion toxins on purified and reconstituted sodium channels by a new toxin derivative.
1. A methyl-4-azidobenzimidyl (MAB) derivative of the alpha-scorpion toxin from Leiurus quinquestriatus (LqTx) specifically labels only the alpha subunit of the rat brain sodium channel in synaptosomes or in purified and reconstituted sodium-channel preparations. 2. Unlike previous photoreactive toxin derivaties, binding and photolabeling by MAB-LqTx are allosterically modulated by tetrodotoxin and batrachotoxin, as observed for native LqTx binding to sodium channels in synaptosomes. 3. Proteolytic cleavage of the alpha subunit photolabeled with MAB-LqTx shows that the label is located within a 60 to 70-kDa protease-resistant core structure in domain I of the sodium-channel alpha subunit. 4. MAB-LqTx will be valuable in further defining the structure-activity relationships at the alpha-scorpion toxin receptor site.
Tejedor
F J
FJ
Department of Pharmacology, University of Washington, Seattle 98195.
Catterall
W A
WA
D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D010777:Photochemistry; D051381:Rats; D011950:Receptors, Cholinergic / Q000032:analysis* / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000032:analysis; D013779:Tetrodotoxin / Q000494:pharmacology
D001496:Batrachotoxins; D011950:Receptors, Cholinergic; D015222:Sodium Channels; C029574:scorpion toxin receptor; D013779:Tetrodotoxin