A novel conotoxin from Conus betulinus, kappa-BtX, unique in cysteine pattern and in function as a specific BK channel modulator
Fan, C.X.; Chen, X.K.; Zhang, C.; Wang, L.X.; Duan, K.L.; He, L.L.; Cao, Y.; Liu, S.Y.; Zhong, M.N.; Ulens, C.; Tytgat, J.; Chen, J.S.; Chi, C.W.; Zhou, Z. (2003). A novel conotoxin from Conus betulinus, kappa-BtX, unique in cysteine pattern and in function as a specific BK channel modulator. J. Biol. Chem. 278(15): 12624-12633. https://dx.doi.org/10.1074/jbc.M210200200 In: Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology: Baltimore, etc.. ISSN 0021-9258; e-ISSN 1083-351X, more |  |
| Keywords | Materials > Hazardous materials > Biological poisons
Conidae J. Fleming, 1822 [WoRMS]
Marine/Coastal |
| Authors | | Top | - Fan, C.X.
- Chen, X.K.
- Zhang, C.
- Wang, L.X.
- Duan, K.L.
| - He, L.L.
- Cao, Y.
- Liu, S.Y.
- Zhong, M.N.
- Ulens, C., more
| - Tytgat, J., more
- Chen, J.S.
- Chi, C.W.
- Zhou, Z.
|
| Abstract | A novel conotoxin, kappa-conotoxin (kappa-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 gamma-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;, K-BtX is a specific modulator of K+ channels; 2) among the K channels, kappa-BtX specifically up-modulates the Ca2+- and voltage-sensitive BK channels (252 47%); 3) its EC50 is 0.7 nm with a single binding site (Hill = 0.88); 4) the time constant of wash-out is 8.3 s; and 5) kappa-BtX has no effect on single channel conductance, but increases the open probability of BK channels. It is concluded that kappa-BtX is a novel specific biotoxin against BK channels. |
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