title: A surface plasmon resonance approach to monitor toxin interactions with an isolated voltage-gated sodium channel paddle motif.
abstract: Animal toxins that inhibit voltage-gated sodium (Na(v)) channel fast inactivation can do so through an interaction with the S3b-S4 helix-turn-helix region, or paddle motif, located in the domain IV voltage sensor. Here, we used surface plasmon resonance (SPR), an optical approach that uses polarized light to measure the refractive index near a sensor surface to which a molecule of interest is attached, to analyze interactions between the isolated domain IV paddle and Na(v) channel-selective α-scorpion toxins. Our SPR analyses showed that the domain IV paddle can be removed from the Na(v) channel and immobilized on sensor chips, and suggest that the isolated motif remains susceptible to animal toxins that target the domain IV voltage sensor. As such, our results uncover the inherent pharmacological sensitivities of the isolated domain IV paddle motif, which may be exploited to develop a label-free SPR approach for discovering ligands that target this region.
authors.affiliation: Centre National de la Recherche Scientifique, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseillle, Unité Mixte de Recherche 7286, Plates-Formes de Recherche en Neurosciences-Centre d'Analyse Protéomique de Marseille, Aix Marseille Université, 13344 Marseille, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.affiliation: Centre National de la Recherche Scientifique, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseillle, Unité Mixte de Recherche 7286, Plates-Formes de Recherche en Neurosciences-Centre d'Analyse Protéomique de Marseille, Aix Marseille Université, 13344 Marseille, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Ferracci
authors.affiliation: Department of Physiology and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205 Department of Physiology and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205 frankbosmans@jhmi.edu pierre-edouard.bougis@univ-amu.fr.
authors.forename: Frank
authors.initials: F
authors.lastname: Bosmans
authors.affiliation: Centre National de la Recherche Scientifique, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseillle, Unité Mixte de Recherche 7286, Plates-Formes de Recherche en Neurosciences-Centre d'Analyse Protéomique de Marseille, Aix Marseille Université, 13344 Marseille, France frankbosmans@jhmi.edu pierre-edouard.bougis@univ-amu.fr.
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Bougis
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008969:Molecular Sequence Data; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology; D020349:Surface Plasmon Resonance / Q000379:methods*; D014981:Xenopus
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; C568253:Scn2A protein, rat; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers