Cobatoxins 1 and 2 from Centruroides noxius Hoffmann constitute a subfamily of potassium-channel-blocking scorpion toxins.
Potassium-channel-blocking scorpion toxins (alpha-K-toxins) have been shown to be valuable tools for the study of potassium channels. Here we report two toxins, cobatoxin 1 and 2, of 32 amino acids, containing three disulphide bridges, that were isolated from the venom of the Mexican scorpion Centruroides noxius. Their primary sequences show less than 40% identity to other alpha-K-toxins. It is therefore proposed that they belong to subfamily 9. The cDNA of cobatoxin 1 encodes a putative signal peptide, a putative short propeptide, the mature peptide and two amino acids that are processed to leave cobatoxin 1 amidated at the C-terminus. In rat brain synaptosomal membranes cobatoxin 1 and cobatoxin 2 bind to a common binding site of alpha-K-toxins with Ki values of 109 pM and 87 pM, respectively. Moreover, they block the Shaker and Kv1.1 K+ channels with moderate affinities, with Kd values of around 0.7 microM and 4.1 microM (Shaker) and 0.5 microM and 1.0 microM (Kv1.1), respectively. A three-dimensional model of cobatoxin 1 was generated and used to interpret the obtained functional data on a structural basis.
Department of Molecular Recognition and Structural Biology, Institute of Biotechnology, Cuernavaca, Mexico.
B
B
Selisko
C
C
Garcia
B
B
Becerril
F
F
Gómez-Lagunas
C
C
Garay
L D
LD
Possani
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D007457:Iodine Radioisotopes; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D026902:Potassium Channel Blockers; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013574:Synaptosomes / Q000378:metabolism
D018076:DNA, Complementary; D007457:Iodine Radioisotopes; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; C113599:cobatoxin 1; C113603:cobatoxin 2; C052567:noxiustoxin