Two-dimensional 1H nuclear magnetic resonance study of AaH IT, an anti-insect toxin from the scorpion androctonus australis hector. Sequential resonance assignments and folding of the polypeptide chain

H. Darbon, C. Weber, Werner Braun

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Sequence-specific nuclear magnetic resonance assignments for the polypeptide backbone and for most of the amino acid side-chain protons, as well as the general folding of AaH IT, are described. AaH IT is a neurotoxin purified from the venom of the scorpion Androctonus australis Hector and is specifically active on the insect nervous system. The secondary structure and the hydrogen-bonding patterns in the regular secondary structure elements are deduced from nuclear Overhauser effects and the sequence locations of the slowly exchanging amide protons. The backbone folding is determined by distance geometry calculations with the DISMAN program. The regular secondary structure includes two and a half turns of α-helix running from residues 21 to 30 and a three-stranded antiparallel β-sheet including peptides 3-5, 34-38, and 41-46. Two tight turns are present, one connecting the end of the α-helix to an external strand of the β-sheet, i.e., turn 31-34, and another connecting this same strand to the central one, i.e., turn 38-41. These structure elements are very similar to the secondary structure reported in single crystals for either variant 3 from the scorpion Centruroides sculpturatus Ewing (CsE V3) or toxin II from the scorpion A. australis Hector (AaH II). The differences in the specificity of these related proteins, which are able to discriminate between mammalian and insect voltage-dependent sodium channels of excitable tissues, are most probably brought about by the position of the C-terminal peptide with regard to a hydrophobic surface common to all scorpion toxins examined thus far. This surface is made of an aromatic cluster that is surrounded by long hydrophobic side-chain residues, as well as the loops protruding out of it. Thus, the interaction of a given scorpion toxin with its receptor might well be governed by the presence of this solvent-exposed hydrophobic surface, whereas adjacent areas modulate the specificity of the interaction.

Original languageEnglish (US)
Pages (from-to)1836-1845
Number of pages10
JournalBiochemistry
Volume30
Issue number7
StatePublished - 1991
Externally publishedYes

Fingerprint

Scorpions
Insects
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Peptides
Protons
Scorpion Venoms
Sodium Channels
Neurotoxins
Neurology
Amides
Hydrogen bonds
Hydrogen Bonding
Single crystals
Running
Tissue
Nervous System
Amino Acids
Geometry
Electric potential

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{fbec7492f68b412c975e8030e47b6140,
title = "Two-dimensional 1H nuclear magnetic resonance study of AaH IT, an anti-insect toxin from the scorpion androctonus australis hector. Sequential resonance assignments and folding of the polypeptide chain",
abstract = "Sequence-specific nuclear magnetic resonance assignments for the polypeptide backbone and for most of the amino acid side-chain protons, as well as the general folding of AaH IT, are described. AaH IT is a neurotoxin purified from the venom of the scorpion Androctonus australis Hector and is specifically active on the insect nervous system. The secondary structure and the hydrogen-bonding patterns in the regular secondary structure elements are deduced from nuclear Overhauser effects and the sequence locations of the slowly exchanging amide protons. The backbone folding is determined by distance geometry calculations with the DISMAN program. The regular secondary structure includes two and a half turns of α-helix running from residues 21 to 30 and a three-stranded antiparallel β-sheet including peptides 3-5, 34-38, and 41-46. Two tight turns are present, one connecting the end of the α-helix to an external strand of the β-sheet, i.e., turn 31-34, and another connecting this same strand to the central one, i.e., turn 38-41. These structure elements are very similar to the secondary structure reported in single crystals for either variant 3 from the scorpion Centruroides sculpturatus Ewing (CsE V3) or toxin II from the scorpion A. australis Hector (AaH II). The differences in the specificity of these related proteins, which are able to discriminate between mammalian and insect voltage-dependent sodium channels of excitable tissues, are most probably brought about by the position of the C-terminal peptide with regard to a hydrophobic surface common to all scorpion toxins examined thus far. This surface is made of an aromatic cluster that is surrounded by long hydrophobic side-chain residues, as well as the loops protruding out of it. Thus, the interaction of a given scorpion toxin with its receptor might well be governed by the presence of this solvent-exposed hydrophobic surface, whereas adjacent areas modulate the specificity of the interaction.",
author = "H. Darbon and C. Weber and Werner Braun",
year = "1991",
language = "English (US)",
volume = "30",
pages = "1836--1845",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - Two-dimensional 1H nuclear magnetic resonance study of AaH IT, an anti-insect toxin from the scorpion androctonus australis hector. Sequential resonance assignments and folding of the polypeptide chain

AU - Darbon, H.

AU - Weber, C.

AU - Braun, Werner

PY - 1991

Y1 - 1991

N2 - Sequence-specific nuclear magnetic resonance assignments for the polypeptide backbone and for most of the amino acid side-chain protons, as well as the general folding of AaH IT, are described. AaH IT is a neurotoxin purified from the venom of the scorpion Androctonus australis Hector and is specifically active on the insect nervous system. The secondary structure and the hydrogen-bonding patterns in the regular secondary structure elements are deduced from nuclear Overhauser effects and the sequence locations of the slowly exchanging amide protons. The backbone folding is determined by distance geometry calculations with the DISMAN program. The regular secondary structure includes two and a half turns of α-helix running from residues 21 to 30 and a three-stranded antiparallel β-sheet including peptides 3-5, 34-38, and 41-46. Two tight turns are present, one connecting the end of the α-helix to an external strand of the β-sheet, i.e., turn 31-34, and another connecting this same strand to the central one, i.e., turn 38-41. These structure elements are very similar to the secondary structure reported in single crystals for either variant 3 from the scorpion Centruroides sculpturatus Ewing (CsE V3) or toxin II from the scorpion A. australis Hector (AaH II). The differences in the specificity of these related proteins, which are able to discriminate between mammalian and insect voltage-dependent sodium channels of excitable tissues, are most probably brought about by the position of the C-terminal peptide with regard to a hydrophobic surface common to all scorpion toxins examined thus far. This surface is made of an aromatic cluster that is surrounded by long hydrophobic side-chain residues, as well as the loops protruding out of it. Thus, the interaction of a given scorpion toxin with its receptor might well be governed by the presence of this solvent-exposed hydrophobic surface, whereas adjacent areas modulate the specificity of the interaction.

AB - Sequence-specific nuclear magnetic resonance assignments for the polypeptide backbone and for most of the amino acid side-chain protons, as well as the general folding of AaH IT, are described. AaH IT is a neurotoxin purified from the venom of the scorpion Androctonus australis Hector and is specifically active on the insect nervous system. The secondary structure and the hydrogen-bonding patterns in the regular secondary structure elements are deduced from nuclear Overhauser effects and the sequence locations of the slowly exchanging amide protons. The backbone folding is determined by distance geometry calculations with the DISMAN program. The regular secondary structure includes two and a half turns of α-helix running from residues 21 to 30 and a three-stranded antiparallel β-sheet including peptides 3-5, 34-38, and 41-46. Two tight turns are present, one connecting the end of the α-helix to an external strand of the β-sheet, i.e., turn 31-34, and another connecting this same strand to the central one, i.e., turn 38-41. These structure elements are very similar to the secondary structure reported in single crystals for either variant 3 from the scorpion Centruroides sculpturatus Ewing (CsE V3) or toxin II from the scorpion A. australis Hector (AaH II). The differences in the specificity of these related proteins, which are able to discriminate between mammalian and insect voltage-dependent sodium channels of excitable tissues, are most probably brought about by the position of the C-terminal peptide with regard to a hydrophobic surface common to all scorpion toxins examined thus far. This surface is made of an aromatic cluster that is surrounded by long hydrophobic side-chain residues, as well as the loops protruding out of it. Thus, the interaction of a given scorpion toxin with its receptor might well be governed by the presence of this solvent-exposed hydrophobic surface, whereas adjacent areas modulate the specificity of the interaction.

UR - http://www.scopus.com/inward/record.url?scp=0025921886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025921886&partnerID=8YFLogxK

M3 - Article

C2 - 1993198

AN - SCOPUS:0025921886

VL - 30

SP - 1836

EP - 1845

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 7

ER -