A Novel Conotoxin from Conus betulinus, κ-BtX, Unique in Cysteine Pattern and in Function as a Specific BK Channel Modulator

• Published in: The Journal of biological chemistry 2003-04, Vol.278 (15), p.12624
• Main Authors: Chong-Xu Fan, Xiao-Ke Chen, Chen Zhang, Li-Xiu Wang, Kai-Lai Duan, Lin-Lin He, Ying Cao, Shang-Yi Liu, Ming-Nai Zhong, Chris Ulens, Jan Tytgat, Ji-Sheng Chen, Cheng-Wu Chi, Zhuan Zhou
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M210200200

A novel conotoxin, κ-conotoxin (κ-BtX), has been purified and characterized from the venom of a worm-hunting cone snail, Conus betulinus . The toxin, with four disulfide bonds, shares no sequence homology with any other conotoxins. Based on a partial amino acid sequence, its cDNA was cloned and sequenced. The deduced sequence consists of a 26-residue putative signal peptide, a 31-residue mature toxin, and a 13-residue extra peptide at the C terminus. The extra peptide is cleaved off by proteinase post-processing. All three Glu residues are γ-carboxylated, one of the two Pro residues is hydroxylated at position 27, and its C-terminal residue is Pro-amidated. The monoisotopic mass of the toxin is 3569.0 Da. Electrophysiological experiments show that: 1) among voltage-gated channels, κ-BtX is a specific modulator of K + channels; 2) among the K channels, κ-BtX specifically up-modulates the Ca 2+ - and voltage-sensitive BK channels (252 ± 47%); 3) its EC 50 is 0.7 n m with a single binding site (Hill = 0.88); 4) the time constant of wash-out is 8.3 s; and 5) κ-BtX has no effect on single channel conductance, but increases the open probability of BK channels. It is concluded that κ-BtX is a novel specific biotoxin against BK channels.