Tst26, a novel peptide blocker of Kv1.2 and Kv1.3 channels from the venom of Tityus stigmurus.
Using high-performance liquid chromatography Tst26, a novel potassium channel blocker peptide, was purified from the venom of the Brazilian scorpion Tityus stigmurus. Its primary structure was determined by means of automatic Edman degradation and mass spectrometry analysis. The peptide is composed of 37 amino acid residues and tightly folded through three disulfide bridges, similar to other K(+) channel blocking peptides purified from scorpion venoms. It contains the "essential dyad" for K(+) channel recognition comprised of a lysine at position 27 and a tyrosine at position 36. Electrophysiological assays revealed that Tst26 blocked hKv1.2 and hKv1.3 channels with high affinity (K(d)=1.9 nM and 10.7 nM, respectively) while it did not affect several other ion channels (mKv1.1, hKv1.4, hKv1.5, hERG, hIKCa1, hBK, hNav1.5) tested at 10 nM concentration. The voltage-dependent steady-state parameters of K(+) channel gating were unaffected by the toxin in both channels, but due to the fast association and dissociation kinetics Tst26 slowed the rate of inactivation of Kv1.3 channels. Based on the primary structure, the systematic nomenclature proposed for this peptide is alpha-KTx 4.6.
Papp
Ferenc
F
Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen 4012, Hungary.
Batista
Cesar V F
CV
Varga
Zoltan
Z
Herceg
Monika
M
Román-González
Sergio A
SA
Gaspar
Rezso
R
Possani
Lourival D
LD
Panyi
Gyorgy
G
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007700:Kinetics; D051663:Kv1.2 Potassium Channel / Q000037:antagonists & inhibitors; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D012604:Scorpion Venoms / Q000737:chemistry*; D012605:Scorpions / Q000737:chemistry*
D051663:Kv1.2 Potassium Channel; D051664:Kv1.3 Potassium Channel; D010455:Peptides; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms