Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor

L. Sellin, Katri Mattila, Arto Annila, J. Schmidt, J. Mcardle, M. Hyvönen, T. Rantala, T. Kivistö

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)

Abstract

The 22-residue toxic peptide (WTX1) from the venom of the Southeast Asian snake Trimeresurus wagleri has multiple sites of action, but its lethal effect has been attributed to blocking the postsynaptic acetylcholine receptor at the neuromuscular junction. The 3-dimensional structure of WTX1 was studied using 2-dimensional nuclear magnetic resonance spectroscopy, circular dichroism, and computer simulations. In aqueous solution, WTX1 was shown to have extended and flexible "tails" defined by a short, rigid disulfide-bonded loop. The flexible regions can undergo structural rearrangement when moved from an aqueous to a less polar environment and may contribute to its effectiveness at different receptor sites. By substituting Gly or Phe for His at position 10, significant effects on the disulfide bond formation and, thereby, the activity of the peptide were observed. These results suggest that even subtle differences in single residues can have profound effects on the dynamics of folding, disulfide bond formation, and activity of this toxic peptide.
Original languageEnglish
Pages (from-to)3-13
Number of pages11
JournalBiophysical Journal
Volume70
Issue number1
DOIs
Publication statusPublished - 1996
MoE publication typeA1 Journal article-refereed

Fingerprint

Trimeresurus
Poisons
Nicotinic Receptors
Disulfides
Peptides
Snakes
Neuromuscular Junction
Venoms
Cholinergic Receptors
Circular Dichroism
Computer Simulation
Tail
Magnetic Resonance Spectroscopy

Cite this

Sellin, L. ; Mattila, Katri ; Annila, Arto ; Schmidt, J. ; Mcardle, J. ; Hyvönen, M. ; Rantala, T. ; Kivistö, T. / Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor. In: Biophysical Journal. 1996 ; Vol. 70, No. 1. pp. 3-13.
@article{42e25f0a0ae241f7ba89984536bf6aec,
title = "Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor",
abstract = "The 22-residue toxic peptide (WTX1) from the venom of the Southeast Asian snake Trimeresurus wagleri has multiple sites of action, but its lethal effect has been attributed to blocking the postsynaptic acetylcholine receptor at the neuromuscular junction. The 3-dimensional structure of WTX1 was studied using 2-dimensional nuclear magnetic resonance spectroscopy, circular dichroism, and computer simulations. In aqueous solution, WTX1 was shown to have extended and flexible {"}tails{"} defined by a short, rigid disulfide-bonded loop. The flexible regions can undergo structural rearrangement when moved from an aqueous to a less polar environment and may contribute to its effectiveness at different receptor sites. By substituting Gly or Phe for His at position 10, significant effects on the disulfide bond formation and, thereby, the activity of the peptide were observed. These results suggest that even subtle differences in single residues can have profound effects on the dynamics of folding, disulfide bond formation, and activity of this toxic peptide.",
author = "L. Sellin and Katri Mattila and Arto Annila and J. Schmidt and J. Mcardle and M. Hyv{\"o}nen and T. Rantala and T. Kivist{\"o}",
year = "1996",
doi = "10.1016/S0006-3495(96)79559-0",
language = "English",
volume = "70",
pages = "3--13",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "1",

}

Sellin, L, Mattila, K, Annila, A, Schmidt, J, Mcardle, J, Hyvönen, M, Rantala, T & Kivistö, T 1996, 'Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor', Biophysical Journal, vol. 70, no. 1, pp. 3-13. https://doi.org/10.1016/S0006-3495(96)79559-0

Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor. / Sellin, L.; Mattila, Katri; Annila, Arto; Schmidt, J.; Mcardle, J.; Hyvönen, M.; Rantala, T.; Kivistö, T.

In: Biophysical Journal, Vol. 70, No. 1, 1996, p. 3-13.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor

AU - Sellin, L.

AU - Mattila, Katri

AU - Annila, Arto

AU - Schmidt, J.

AU - Mcardle, J.

AU - Hyvönen, M.

AU - Rantala, T.

AU - Kivistö, T.

PY - 1996

Y1 - 1996

N2 - The 22-residue toxic peptide (WTX1) from the venom of the Southeast Asian snake Trimeresurus wagleri has multiple sites of action, but its lethal effect has been attributed to blocking the postsynaptic acetylcholine receptor at the neuromuscular junction. The 3-dimensional structure of WTX1 was studied using 2-dimensional nuclear magnetic resonance spectroscopy, circular dichroism, and computer simulations. In aqueous solution, WTX1 was shown to have extended and flexible "tails" defined by a short, rigid disulfide-bonded loop. The flexible regions can undergo structural rearrangement when moved from an aqueous to a less polar environment and may contribute to its effectiveness at different receptor sites. By substituting Gly or Phe for His at position 10, significant effects on the disulfide bond formation and, thereby, the activity of the peptide were observed. These results suggest that even subtle differences in single residues can have profound effects on the dynamics of folding, disulfide bond formation, and activity of this toxic peptide.

AB - The 22-residue toxic peptide (WTX1) from the venom of the Southeast Asian snake Trimeresurus wagleri has multiple sites of action, but its lethal effect has been attributed to blocking the postsynaptic acetylcholine receptor at the neuromuscular junction. The 3-dimensional structure of WTX1 was studied using 2-dimensional nuclear magnetic resonance spectroscopy, circular dichroism, and computer simulations. In aqueous solution, WTX1 was shown to have extended and flexible "tails" defined by a short, rigid disulfide-bonded loop. The flexible regions can undergo structural rearrangement when moved from an aqueous to a less polar environment and may contribute to its effectiveness at different receptor sites. By substituting Gly or Phe for His at position 10, significant effects on the disulfide bond formation and, thereby, the activity of the peptide were observed. These results suggest that even subtle differences in single residues can have profound effects on the dynamics of folding, disulfide bond formation, and activity of this toxic peptide.

U2 - 10.1016/S0006-3495(96)79559-0

DO - 10.1016/S0006-3495(96)79559-0

M3 - Article

VL - 70

SP - 3

EP - 13

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 1

ER -