Blockage of human T lymphocyte Kv1.3 channels by Pi1, a novel class of scorpion toxin.
Using the patch-clamp technique we determined that Pandinus imperator toxin Pi1, a recently described peptide toxin having four disulfide bridges instead of the usual three in scorpion toxins, blocked Kv1.3 channels of human T lymphocytes from the extracellular side with a 1:1 stoichiometry. Kv1.3 block was instantaneous and removable with toxin-free extracellular solution. The toxin did not influence activation or inactivation of the channels. We found that Pi1 blocked Kv1.3 with less affinity (K(d) = 11.4 nM) than the structurally related three disulfide bridge containing toxins Pi2 (50 pM) and Pi3 (0.5 nM). The fourth disulfide bridge in Pi1 had no influence on the channel binding ability of the toxin; the less effective block was due to differences in amino acid side chain properties at positions 11 and 35.
Péter
M
M
Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, Debrecen, 4012, Hungary.
Hajdu
P
P
Varga
Z
Z
Damjanovich
S
S
Possani
L D
LD
Panyi
G
G
Gáspár
R
R
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D004220:Disulfides; D006801:Humans; D007700:Kinetics; D051664:Kv1.3 Potassium Channel; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology*; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors
D000596:Amino Acids; D004220:Disulfides; C496973:KCNA3 protein, human; D051664:Kv1.3 Potassium Channel; C104751:Pi1 toxin; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D011188:Potassium