{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T21:56:45Z","timestamp":1773957405153,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,22]],"date-time":"2005-02-22T00:00:00Z","timestamp":1109030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b4\u2010PaluIT1 and \u03b4\u2010paluIT2 are toxins purified from the venom of the spider <jats:italic>Paracoelotes luctuosus<\/jats:italic>. Similar in sequence to \u03bc\u2010agatoxins from <jats:italic>Agelenopsis aperta<\/jats:italic>, their pharmacological target is the voltage\u2010gated insect sodium channel, of which they alter the inactivation properties in a way similar to \u03b1\u2010scorpion toxins, but they bind on site 4 in a way similar to \u03b2\u2010scorpion toxins. We determined the solution structure of the two toxins by use of two\u2010dimensional nuclear magnetic resonance (NMR) techniques followed by distance geometry and molecular dynamics. The structures of \u03b4\u2010paluIT1 and \u03b4\u2010paluIT2 belong to the inhibitory cystine knot structural family, i.e. a compact disulfide\u2010bonded core from which four loops emerge. \u03b4\u2010PaluIT1 and \u03b4\u2010paluIT2 contain respectively two\u2010 and three\u2010stranded anti\u2010parallel \u03b2\u2010sheets 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\u2010gated sodium channels by these toxins involves the \u03b2\u2010sheet, 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\u2010gated sodium channel, <jats:italic>para<\/jats:italic>, heterologuously co\u2010expressed with the tipE subunit in <jats:italic>Xenopus laevis<\/jats:italic> oocytes, that \u03b4\u2010paluIT1 and \u03b4\u2010paluIT2 procure an increase of Na<jats:sup>+<\/jats:sup> current. \u03b4\u2010PaluIT1\u2010OH seems to have less effect when the same concentrations are used. Proteins 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.20424","type":"journal-article","created":{"date-parts":[[2005,2,22]],"date-time":"2005-02-22T21:46:46Z","timestamp":1109108806000},"page":"368-379","source":"Crossref","is-referenced-by-count":30,"title":["Solution structure of two insect\u2010specific spider toxins and their pharmacological interaction with the insect voltage\u2010gated Na<sup>+<\/sup> 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