Structural highlights
Function
[CO17A_CONPU] Kappa-conotoxins bind and inhibit voltage-gated potassium channels (Kv). This toxin inhibits the Shaker channel from insects. The interaction site between the Shaker channel and this toxin is within the S5-S6 loop of the Shaker channel. In fish, this toxin induces hyperactivity, followed by continuous contraction and extension of major fins, without immobilization or death. Injection of this peptide together with the delta-conotoxin PVIA causes the sudden tetanus of prey (STOP) syndrome, which is a single, lethal "fin-pop" in envenomed fish. In mice, induces hyperactivity.[1] [2] [3] [4]
Publication Abstract from PubMed
BACKGROUND: kappa-PVIIA is a 27-residue polypeptide isolated from the venom of Conus purpurascens and is the first member of a new class of conotoxins that block potassium channels. By comparison to other ion channels of eukaryotic cell membranes, voltage-sensitive potassium channels are relatively simple and methodology has been developed for mapping their interactions with small-peptide toxins. PVIIA, therefore, is a valuable new probe of potassium channel structure. This study of the solution structure and mode of channel binding of PVIIA forms the basis for mapping the interacting residues at the conotoxin-ion channel interface. RESULTS: The three-dimensional structure of PVIIA resembles the triple-stranded beta sheet/cystine-knot motif formed by a number of toxic and inhibitory peptides. Subtle structural differences, predominantly in loops 2 and 4, are observed between PVIIA and other conotoxins with similar structural frameworks, however. Electrophysiological binding data suggest that PVIIA blocks channel currents by binding in a voltage-sensitive manner to the external vestibule and occluding the pore. Comparison of the electrostatic surface of PVIIA with that of the well-characterised potassium channel blocker charybdotoxin suggests a likely binding orientation for PVIIA. CONCLUSIONS: Although the structure of PVIIA is considerably different to that of the alphaK scorpion toxins, it has a similar mechanism of channel blockade. On the basis of a comparison of the structures of PVIIA and charybdotoxin, we suggest that Lys19 of PVIIA is the residue which is responsible for physically occluding the pore of the potassium channel.
Solution structure and proposed binding mechanism of a novel potassium channel toxin kappa-conotoxin PVIIA.,Scanlon MJ, Naranjo D, Thomas L, Alewood PF, Lewis RJ, Craik DJ Structure. 1997 Dec 15;5(12):1585-97. PMID:9438859[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Terlau H, Boccaccio A, Olivera BM, Conti F. The block of Shaker K+ channels by kappa-conotoxin PVIIA is state dependent. J Gen Physiol. 1999 Jul;114(1):125-40. PMID:10398696
- ↑ Naranjo D. Inhibition of single Shaker K channels by kappa-conotoxin-PVIIA. Biophys J. 2002 Jun;82(6):3003-11. PMID:12023223 doi:http://dx.doi.org/S0006-3495(02)75641-5
- ↑ Terlau H, Shon KJ, Grilley M, Stocker M, Stuhmer W, Olivera BM. Strategy for rapid immobilization of prey by a fish-hunting marine snail. Nature. 1996 May 9;381(6578):148-51. PMID:12074021 doi:http://dx.doi.org/10.1038/381148a0
- ↑ Shon KJ, Stocker M, Terlau H, Stuhmer W, Jacobsen R, Walker C, Grilley M, Watkins M, Hillyard DR, Gray WR, Olivera BM. kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel. J Biol Chem. 1998 Jan 2;273(1):33-8. PMID:9417043
- ↑ Scanlon MJ, Naranjo D, Thomas L, Alewood PF, Lewis RJ, Craik DJ. Solution structure and proposed binding mechanism of a novel potassium channel toxin kappa-conotoxin PVIIA. Structure. 1997 Dec 15;5(12):1585-97. PMID:9438859
