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PDBsum entry 1v91
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References listed in PDB file
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Key reference
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Title
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Solution structure of two insect-Specific spider toxins and their pharmacological interaction with the insect voltage-Gated na+ channel.
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Authors
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G.Ferrat,
F.Bosmans,
J.Tytgat,
C.Pimentel,
B.Chagot,
N.Gilles,
T.Nakajima,
H.Darbon,
G.Corzo.
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Ref.
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Proteins, 2005,
59,
368-379.
[DOI no: ]
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PubMed id
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Abstract
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Delta-paluIT1 and delta-paluIT2 are toxins purified from the venom of the spider
Paracoelotes luctuosus. Similar in sequence to mu-agatoxins from Agelenopsis
aperta, their pharmacological target is the voltage-gated insect sodium channel,
of which they alter the inactivation properties in a way similar to
alpha-scorpion toxins, but they bind on site 4 in a way similar to beta-scorpion
toxins. We determined the solution structure of the two toxins by use of
two-dimensional nuclear magnetic resonance (NMR) techniques followed by distance
geometry and molecular dynamics. The structures of delta-paluIT1 and
delta-paluIT2 belong to the inhibitory cystine knot structural family, i.e. a
compact disulfide-bonded core from which four loops emerge. Delta-paluIT1 and
delta-paluIT2 contain respectively two- and three-stranded anti-parallel
beta-sheets as unique secondary structure. We compare the structure and the
electrostatic anisotropy of those peptides to other sodium and calcium channel
toxins, analyze the topological juxtaposition of key functional residues, and
conclude that the recognition of insect voltage-gated sodium channels by these
toxins involves the beta-sheet, in addition to loops I and IV. Besides the
position of culprit residues on the molecular surface, difference in dipolar
moment orientation is another determinant of receptor binding and biological
activity differences. We also demonstrate by electrophysiological experiments on
the cloned insect voltage-gated sodium channel, para, heterologuously
co-expressed with the tipE subunit in Xenopus laevis oocytes, that delta-paluIT1
and delta-paluIT2 procure an increase of Na+ current. delta-PaluIT1-OH seems to
have less effect when the same concentrations are used.
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Figure 3.
Figure 3. Superimposition of the 20 best solution structures of
(A)  -paluIT1
and (B) -paluIT2
and molscript representations of the average structures. (C)
Molscript representation of the  -aga
IV model.
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Figure 4.
Figure 4. Relative orientations of the dipolar moments of -paluIT1-OH,
-paluIT1,
and -paluIT2.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2005,
59,
368-379)
copyright 2005.
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