Novel α-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1 K+ channels of T cells

Timoteo Olamendi-Portugal, Sándor Somodi, Juan Antonio Fernández, Fernando Z. Zamudio, Baltazar Becerril, Zoltán Varga, G. Panyi, R. Gáspár, Lourival D. Possani

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 α-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 (α-KTx 2.8), Ce2 (α-KTX2.9) and Ce4 (α-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 0.98 nM 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.

Original languageEnglish
Pages (from-to)418-429
Number of pages12
JournalToxicon
Volume46
Issue number4
DOIs
Publication statusPublished - Sep 15 2005

Fingerprint

Scorpion Venoms
T-cells
T-Lymphocytes
Peptides
Names
Voltage-Gated Potassium Channels
Scorpions
Amino Acids
Calcium-Activated Potassium Channels
Clamping devices
T-Lymphocyte Subsets
Set theory
Disulfides
Amino Acid Sequence
Assays
Molecular Weight
Molecular weight
Degradation
Electric potential

Keywords

  • α-KTx
  • Centruroides elegans
  • Kv1.3 channel
  • Scorpion toxin
  • T lymphocytes

ASJC Scopus subject areas

  • Toxicology

Cite this

Olamendi-Portugal, T., Somodi, S., Fernández, J. A., Zamudio, F. Z., Becerril, B., Varga, Z., ... Possani, L. D. (2005). Novel α-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1 K+ channels of T cells. Toxicon, 46(4), 418-429. https://doi.org/10.1016/j.toxicon.2005.06.001

Novel α-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1 K+ channels of T cells. / Olamendi-Portugal, Timoteo; Somodi, Sándor; Fernández, Juan Antonio; Zamudio, Fernando Z.; Becerril, Baltazar; Varga, Zoltán; Panyi, G.; Gáspár, R.; Possani, Lourival D.

In: Toxicon, Vol. 46, No. 4, 15.09.2005, p. 418-429.

Research output: Contribution to journalArticle

Olamendi-Portugal, Timoteo ; Somodi, Sándor ; Fernández, Juan Antonio ; Zamudio, Fernando Z. ; Becerril, Baltazar ; Varga, Zoltán ; Panyi, G. ; Gáspár, R. ; Possani, Lourival D. / Novel α-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1 K+ channels of T cells. In: Toxicon. 2005 ; Vol. 46, No. 4. pp. 418-429.
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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 α-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 (α-KTx 2.8), Ce2 (α-KTX2.9) and Ce4 (α-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 0.98 nM 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.",
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T1 - Novel α-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1 K+ channels of T cells

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AU - Somodi, Sándor

AU - Fernández, Juan Antonio

AU - Zamudio, Fernando Z.

AU - Becerril, Baltazar

AU - Varga, Zoltán

AU - Panyi, G.

AU - Gáspár, R.

AU - Possani, Lourival D.

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AB - 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 α-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 (α-KTx 2.8), Ce2 (α-KTX2.9) and Ce4 (α-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 0.98 nM 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.

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