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Published online before print February 1, 2006, 10.1110/ps.051860606
Protein Science (2006), 15:628-634. Published by Cold Spring Harbor Laboratory Press. Copyright © 2006 The Protein Society
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PROTEIN STRUCTURE REPORT

Solution structure of PcFK1, a spider peptide active against Plasmodium falciparum

Cyril Pimentel1, Soo-Jin Choi2, Benjamin Chagot1, Catherine Guette3, Jean-Michel Camadro2 and Hervé Darbon1

1 Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique (CNRS) UMR 6098 and Universités d’Aix-Marseille I and II, 13402 Marseille Cedex 20, France
2 Ingénierie des Protéines et Contr⊚le Métabolique, Département de Biologie des Génomes, Institut Jacques Monod, UMR 7592, Centre National de la Recherche Scientifique—Universités Paris 6 & 7, 75251 Paris Cedex 05, France
3 Substances d’Origine Naturelle et Analogues Structuraux (SONAS), UPRES EA 921, UFR Sciences pharmaceutiques et ingénierie de la santé, 49045 Angers Cedex 01, France

(RECEIVED September 23, 2005; FINAL REVISION November 28, 2005; ACCEPTED December 7, 2005)

Psalmopeotoxin I (PcFK1) is a 33-amino-acid residue peptide isolated from the venom of the tarantula Psalmopoeus cambridgei. It has been recently shown to possess strong antiplasmodial activity against the intra-erythrocyte stage of Plasmodium falciparum in vitro. Although the molecular target for PcFK1 is not yet determined, this peptide does not lyse erythrocytes, is not cytotoxic to nucleated mammalian cells, and does not inhibit neuromuscular function. We investigated the structural properties of PcFK1 to help understand the unique mechanism of action of this peptide and to enhance its utility as a lead compound for rational development of new antimalarial drugs. In this paper, we have determined the three-dimensional solution structure by 1H two-dimensional NMR means of recombinant PcFK1, which is shown to belong to the ICK structural superfamily with structural determinants common to several neurotoxins acting as ion channels effectors.

Keywords: Psalmopoeus cambridgei; PcFK1; spider toxin; structure determination; Plasmodium; malaria; NMR

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.051860606.

Reprint requests to: Hervé Darbon, AFMB, CNRS UMR 6098 and Universités d’Aix-Marseille I and II, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France; e-mail: Herve.Darbon{at}afmb.univ-mrs.fr; fax: +33 (0)4-91-16-45-16.


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