Site of covalent attachment of alpha-scorpion toxin derivatives in domain I of the sodium channel alpha subunit.
Purified and reconstituted sodium channels from rat brain have been photoaffinity labeled with a photoactivable derivative of the alpha-scorpion toxin V from Leiurus quinquestriatus (LqTx). A battery of sequence-specific antibodies has been used to determine which of the peptides produced by chemical and enzymatic cleavage of the photolabeled sodium-channel alpha subunit contain covalently attached LqTx. Nearly all of the covalently attached LqTx is found within homologous domain I. Two site-directed antisera, which recognize residues 317 to 335 and residues 382 to 400, respectively, specifically immunoprecipitate a 14-kDa peptide produced by CNBr digestion to which LqTx is covalently attached. It is proposed that a portion of the receptor site for alpha-scorpion toxins is formed by peptide segment(s) between amino acid residues 335 and 378 which is located in an extracellular loop between transmembrane helices S5 and S6 of homologous domain I of the sodium channel alpha subunit.
Tejedor
F J
FJ
Department of Pharmacology, University of Washington, Seattle 98195.
Catterall
W A
WA
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D012604:Scorpion Venoms / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D012604:Scorpion Venoms; D015222:Sodium Channels