PDBsum entry 1v91

Toxin

PDB id: 1v91

Contents

Protein chain

38 a.a. *

* Residue conservation analysis

PDB id:

1v91

Name:

Toxin

Title:

Solution structure of insectidal toxin delta-paluit2-nh2

Structure:

Delta-palutoxin it2. Chain: a. Synonym: delta-paluit2

Source:

Paracoelotes luctuosus. Organism_taxid: 185217

NMR struc:

20 models

Authors:

G.Ferrat,F.Bosmans,J.Tytgat,C.Pimentel,B.Chagot,T.Nakajima,H.Darbon, G.Corzo

Key ref:

G.Ferrat et al. (2005). Solution structure of two insect-specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel. Proteins, 59, 368-379. PubMed id: 15726637 DOI: 10.1002/prot.20424

Date:

19-Jan-04 Release date: 29-Mar-05

Protein chain

P83257  (T3D1B_PIRLC) -  Delta-amaurobitoxin-Pl1b from Pireneitega luctuosa

Seq: 37 a.a.

Struc: 38 a.a.

DOI no: 10.1002/prot.20424

Proteins 59:368-379 (2005)

PubMed id: 15726637

Solution structure of two insect-specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel.

G.Ferrat, F.Bosmans, J.Tytgat, C.Pimentel, B.Chagot, N.Gilles, T.Nakajima, H.Darbon, G.Corzo.

ABSTRACT

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.

Selected figure(s)

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.

Figure 4.
Figure 4. Relative orientations of the dipolar moments of -paluIT1-OH, -paluIT1, and -paluIT2.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2005, 59, 368-379) copyright 2005.

Figures were selected by an automated process.