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PDBsum entry 1axh
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* Residue conservation analysis
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Nat Struct Biol
4:559-566
(1997)
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PubMed id:
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The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1, from the venom of an Australian funnel web spider.
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J.I.Fletcher,
R.Smith,
S.I.O'Donoghue,
M.Nilges,
M.Connor,
M.E.Howden,
M.J.Christie,
G.F.King.
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ABSTRACT
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A family of potent insecticidal toxins has recently been isolated from the venom
of Australian funnel web spiders. Among these is the 37-residue peptide
omega-atracotoxin-HV1 (omega-ACTX-HV1) from Hadronyche versuta. We have
chemically synthesized and folded omega-ACTX-HV1, shown that it is neurotoxic,
ascertained its disulphide bonding pattern, and determined its three-dimensional
solution structure using NMR spectroscopy. The structure consists of a
solvent-accessible beta-hairpin protruding from a disulphide-bonded globular
core comprising four beta-turns. The three intramolecular disulphide bonds from
a cystine knot motif similar to that seen in several other neurotoxic peptides.
Despite limited sequence identity, omega-ACTX-HV1 displays significant
structural homology with the omega-agatoxins and omega-conotoxins, both of which
are vertebrate calcium channel antagonists; however, in contrast with these
toxins, we show that omega-ACTX-HV1 inhibits insect, but not mammalian,
voltage-gated calcium channel currents.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Comis,
M.Tyler,
E.Mylecharane,
I.Spence,
and
M.Howden
(2009).
Immunization with a synthetic robustoxin derivative lacking disulphide bridges protects against a potentially lethal challenge with funnel-web spider (Atrax robustus) venom.
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J Biosci,
34,
35-44.
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C.Romeo,
L.Di Francesco,
M.Oliverio,
P.Palazzo,
G.R.Massilia,
P.Ascenzi,
F.Polticelli,
and
M.E.Schininà
(2008).
Conus ventricosus venom peptides profiling by HPLC-MS: a new insight in the intraspecific variation.
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J Sep Sci,
31,
488-498.
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S.J.Gunning,
F.Maggio,
M.J.Windley,
S.M.Valenzuela,
G.F.King,
and
G.M.Nicholson
(2008).
The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca) channels.
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FEBS J,
275,
4045-4059.
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Y.Han,
F.Huang,
H.Jiang,
L.Liu,
Q.Wang,
Y.Wang,
X.Shao,
C.Chi,
W.Du,
and
C.Wang
(2008).
Purification and structural characterization of a D-amino acid-containing conopeptide, conomarphin, from Conus marmoreus.
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FEBS J,
275,
1976-1987.
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PDB codes:
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N.Fujitani,
T.Kouno,
T.Nakahara,
K.Takaya,
T.Osaki,
S.Kawabata,
M.Mizuguchi,
T.Aizawa,
M.Demura,
S.Nishimura,
and
K.Kawano
(2007).
The solution structure of horseshoe crab antimicrobial peptide tachystatin B with an inhibitory cystine-knot motif.
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J Pept Sci,
13,
269-279.
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PDB codes:
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S.A.Khan,
Y.Zafar,
R.W.Briddon,
K.A.Malik,
and
Z.Mukhtar
(2006).
Spider venom toxin protects plants from insect attack.
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Transgenic Res,
15,
349-357.
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G.Ferrat,
F.Bosmans,
J.Tytgat,
C.Pimentel,
B.Chagot,
N.Gilles,
T.Nakajima,
H.Darbon,
and
G.Corzo
(2005).
Solution structure of two insect-specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel.
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Proteins,
59,
368-379.
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PDB codes:
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S.Kozlov,
A.Malyavka,
B.McCutchen,
A.Lu,
E.Schepers,
R.Herrmann,
and
E.Grishin
(2005).
A novel strategy for the identification of toxinlike structures in spider venom.
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Proteins,
59,
131-140.
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C.Bernard,
G.Corzo,
S.Adachi-Akahane,
G.Foures,
K.Kanemaru,
Y.Furukawa,
T.Nakajima,
and
H.Darbon
(2004).
Solution structure of ADO1, a toxin extracted from the saliva of the assassin bug, Agriosphodrus dohrni.
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Proteins,
54,
195-205.
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PDB code:
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H.W.Tedford,
N.Gilles,
A.Ménez,
C.J.Doering,
G.W.Zamponi,
and
G.F.King
(2004).
Scanning mutagenesis of omega-atracotoxin-Hv1a reveals a spatially restricted epitope that confers selective activity against insect calcium channels.
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J Biol Chem,
279,
44133-44140.
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F.Maggio,
and
G.F.King
(2002).
Scanning mutagenesis of a Janus-faced atracotoxin reveals a bipartite surface patch that is essential for neurotoxic function.
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J Biol Chem,
277,
22806-22813.
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K.J.Rosengren,
D.Wilson,
N.L.Daly,
P.F.Alewood,
and
D.J.Craik
(2002).
Solution structures of the cis- and trans-Pro30 isomers of a novel 38-residue toxin from the venom of Hadronyche Infensa sp. that contains a cystine-knot motif within its four disulfide bonds.
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Biochemistry,
41,
3294-3301.
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PDB codes:
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N.Gilles,
G.Harrison,
I.Karbat,
M.Gurevitz,
G.M.Nicholson,
and
D.Gordon
(2002).
Variations in receptor site-3 on rat brain and insect sodium channels highlighted by binding of a funnel-web spider delta-atracotoxin.
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Eur J Biochem,
269,
1500-1510.
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Q.Shu,
S.Y.Lu,
X.C.Gu,
and
S.P.Liang
(2002).
The structure of spider toxin huwentoxin-II with unique disulfide linkage: evidence for structural evolution.
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Protein Sci,
11,
245-252.
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PDB code:
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X.H.Wang,
M.Connor,
D.Wilson,
H.I.Wilson,
G.M.Nicholson,
R.Smith,
D.Shaw,
J.P.Mackay,
P.F.Alewood,
M.J.Christie,
and
G.F.King
(2001).
Discovery and structure of a potent and highly specific blocker of insect calcium channels.
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J Biol Chem,
276,
40306-40312.
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PDB codes:
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E.Zlotkin,
Y.Fishman,
and
M.Elazar
(2000).
AaIT: from neurotoxin to insecticide.
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Biochimie,
82,
869-881.
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G.Corzo,
P.Escoubas,
M.Stankiewicz,
M.Pelhate,
C.P.Kristensen,
and
T.Nakajima
(2000).
Isolation, synthesis and pharmacological characterization of delta-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae).
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Eur J Biochem,
267,
5783-5795.
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J.M.Hill,
P.F.Alewood,
and
D.J.Craik
(2000).
Conotoxin TVIIA, a novel peptide from the venom of Conus tulipa 2. Three-dimensional solution structure.
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Eur J Biochem,
267,
4649-4657.
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PDB code:
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Z.Chen,
P.Xu,
J.R.Barbier,
G.Willick,
and
F.Ni
(2000).
Solution structure of the osteogenic 1-31 fragment of the human parathyroid hormone.
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Biochemistry,
39,
12766-12777.
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PDB code:
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B.Gilquin,
A.Lecoq,
F.Desné,
M.Guenneugues,
S.Zinn-Justin,
and
A.Ménez
(1999).
Conformational and functional variability supported by the BPTI fold: solution structure of the Ca2+ channel blocker calcicludine.
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Proteins,
34,
520-532.
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PDB code:
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E.Grishin
(1999).
Polypeptide neurotoxins from spider venoms.
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Eur J Biochem,
264,
276-280.
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J.I.Fletcher,
A.J.Dingley,
R.Smith,
M.Connor,
M.J.Christie,
and
G.F.King
(1999).
High-resolution solution structure of gurmarin, a sweet-taste-suppressing plant polypeptide.
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Eur J Biochem,
264,
525-533.
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PDB codes:
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P.J.Erbel,
Y.Karimi-Nejad,
T.De Beer,
R.Boelens,
J.P.Kamerling,
and
J.F.Vliegenthart
(1999).
Solution structure of the alpha-subunit of human chorionic gonadotropin.
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Eur J Biochem,
260,
490-498.
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PDB code:
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X.Wang,
R.Smith,
J.I.Fletcher,
H.Wilson,
C.J.Wood,
M.E.Howden,
and
G.F.King
(1999).
Structure-function studies of omega-atracotoxin, a potent antagonist of insect voltage-gated calcium channels.
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Eur J Biochem,
264,
488-494.
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M.J.Little,
C.Zappia,
N.Gilles,
M.Connor,
M.I.Tyler,
M.F.Martin-Eauclaire,
D.Gordon,
and
G.M.Nicholson
(1998).
delta-Atracotoxins from australian funnel-web spiders compete with scorpion alpha-toxin binding but differentially modulate alkaloid toxin activation of voltage-gated sodium channels.
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J Biol Chem,
273,
27076-27083.
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J.I.Fletcher,
B.E.Chapman,
J.P.Mackay,
M.E.Howden,
and
G.F.King
(1997).
The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel.
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Structure,
5,
1525-1535.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
