title: Novel alpha-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1 K+ channels of T cells.
abstract: From the venom of the Mexican scorpion Centruroides elegans Thorell five peptides were isolated to homogeneity by chromatographic procedures and their full amino acid sequence was determined by automatic Edman degradation. They all belong to the Noxiustoxin subfamily of scorpion toxins and were given the systematic names alpha-KTx 2.8 to 2.12, with trivial names Ce1 to Ce5, respectively. They have 39 amino acid residues, except for Ce3 which has only 38, but all of them have three disulfide bridges, and have molecular weights of 4255, 4267, 4249, 4295 and 4255 atomic mass units, respectively for Ce1 to Ce5. The C-terminal residues of Ce2, Ce4 and Ce5 were found to be amidated. The electrophysiological assay (whole-cell patch-clamp) showed that out of the five peptides, Ce1 (alpha-KTx 2.8), Ce2 (alpha-KTX2.9) and Ce4 (alpha-KTx 2.11) were effective blockers of Kv1.3 channels of human T lymphocytes, whereas these peptides did not inhibit the Ca2+-activated K+ channels (IKCa1) of the same cells. The equilibrium dissociation constants of these peptides for Kv1.3 were 0.70, 0.25 and 0.98nM for Ce1, Ce2 and Ce4, respectively. Furthermore, toxins Ce1, Ce2 and Ce4 practically did not inhibit the related voltage gated Shaker K+ channels, and rKv2.1 channels of the Shab family. The high affinity blockage of Kv1.3 channels by these peptides and their selectivity for Kv1.3 over IKCa1 may have significance in the development of novel tools for suppressing the function of those T cell subsets whose proliferation critically depends on the activity of Kv1.3 channels.
authors: Department of Molecular Medicine and Bioprocesses, Institute of Biotechnology, National Autonomous University of Mexico, Avenida Universidad, 2001, Apartado Postal 510-3, Cuernavaca 62210, Mexico.
authors: Timoteo
authors: T
authors: Olamendi-Portugal
authors: Sándor
authors: S
authors: Somodi
authors: Juan Antonio
authors: JA
authors: Fernández
authors: Fernando Z
authors: FZ
authors: Zamudio
authors: Baltazar
authors: B
authors: Becerril
authors: Zoltán
authors: Z
authors: Varga
authors: Gyorgy
authors: G
authors: Panyi
authors: Rezso
authors: R
authors: Gáspár
authors: Lourival D
authors: LD
authors: Possani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001499:Bayes Theorem; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D013058:Mass Spectrometry; D008800:Mexico; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009943:Organophosphorus Compounds; D010455:Peptides / Q000235:genetics* / Q000378:metabolism* / Q000633:toxicity; D010802:Phylogeny; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity; D012605:Scorpions; D020539:Sequence Analysis, Protein; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: C043517:2-(4-isothiocyanatophenoxy)-1,3,2-dioxaphosphinene 2-oxide; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D051664:Kv1.3 Potassium Channel; D009943:Organophosphorus Compounds; D010455:Peptides; D012604:Scorpion Venoms