Looking over toxin-K + channel interactions. clues from the structural and functional characterization of α-KTx Toxin Tc32, a Kv1.3 Channel Blocker

Eliana G. Stehling, Mauricio L. Sforça, Nilson I T Zanchin, Sérgio Oyama, Angela Pignatelli, Ottorino Belluzzi, Eugenia Polverini, Romina Corsini, Alberto Spisni, Thelma A. Pertinhez

Research output: Contribution to journalArticle

Abstract

α-KTx toxin Tc32, from the Amazonian scorpion Tityus cambridgei, lacks the dyad motif, including Lys27, characteristic of the family and generally associated with channel blockage. The toxin has been cloned and expressed for the first time. Electrophysiological experiments, by showing that the recombinant form blocks Kv1.3 channels of olfactory bulb periglomerular cells like the natural Tc32 toxin, when tested on the Kv1.3 channel of human T lymphocytes, confirmed it is in an active fold. The nuclear magnetic resonance-derived structure revealed it exhibits an α/β scaffold typical of the members of the α-KTx family. TdK2 and TdK3, all belonging to the same α-KTx 18 subfamily, share significant sequence identity with Tc32 but diverse selectivity and affinity for Kv1.3 and Kv1.1 channels. To gain insight into the structural features that may justify those differences, we used the recombinant Tc32 nuclear magnetic resonance-derived structure to model the other two toxins, for which no experimental structure is available. Their interaction with Kv1.3 and Kv1.1 has been investigated by means of docking simulations. The results suggest that differences in the electrostatic features of the toxins and channels, in their contact surfaces, and in their total dipole moment orientations govern the affinity and selectivity of toxins. In addition, we found that, regardless of whether the dyad motif is present, it is always a Lys side chain that physically blocks the channels, irrespective of its position in the toxin sequence.

Original languageEnglish
Pages (from-to)1885-1894
Number of pages10
JournalBiochemistry
Volume51
Issue number9
DOIs
Publication statusPublished - Mar 6 2012

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Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Scorpions
T-cells
Olfactory Bulb
Dipole moment
Static Electricity
Scaffolds
Electrostatics
T-Lymphocytes
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Stehling, E. G., Sforça, M. L., Zanchin, N. I. T., Oyama, S., Pignatelli, A., Belluzzi, O., ... Pertinhez, T. A. (2012). Looking over toxin-K + channel interactions. clues from the structural and functional characterization of α-KTx Toxin Tc32, a Kv1.3 Channel Blocker. Biochemistry, 51(9), 1885-1894. https://doi.org/10.1021/bi201713z

Looking over toxin-K + channel interactions. clues from the structural and functional characterization of α-KTx Toxin Tc32, a Kv1.3 Channel Blocker. / Stehling, Eliana G.; Sforça, Mauricio L.; Zanchin, Nilson I T; Oyama, Sérgio; Pignatelli, Angela; Belluzzi, Ottorino; Polverini, Eugenia; Corsini, Romina; Spisni, Alberto; Pertinhez, Thelma A.

In: Biochemistry, Vol. 51, No. 9, 06.03.2012, p. 1885-1894.

Research output: Contribution to journalArticle

Stehling, EG, Sforça, ML, Zanchin, NIT, Oyama, S, Pignatelli, A, Belluzzi, O, Polverini, E, Corsini, R, Spisni, A & Pertinhez, TA 2012, 'Looking over toxin-K + channel interactions. clues from the structural and functional characterization of α-KTx Toxin Tc32, a Kv1.3 Channel Blocker', Biochemistry, vol. 51, no. 9, pp. 1885-1894. https://doi.org/10.1021/bi201713z
Stehling, Eliana G. ; Sforça, Mauricio L. ; Zanchin, Nilson I T ; Oyama, Sérgio ; Pignatelli, Angela ; Belluzzi, Ottorino ; Polverini, Eugenia ; Corsini, Romina ; Spisni, Alberto ; Pertinhez, Thelma A. / Looking over toxin-K + channel interactions. clues from the structural and functional characterization of α-KTx Toxin Tc32, a Kv1.3 Channel Blocker. In: Biochemistry. 2012 ; Vol. 51, No. 9. pp. 1885-1894.
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AU - Zanchin, Nilson I T

AU - Oyama, Sérgio

AU - Pignatelli, Angela

AU - Belluzzi, Ottorino

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AU - Spisni, Alberto

AU - Pertinhez, Thelma A.

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