title: Molecular surface of tarantula toxins interacting with voltage sensors in K(v) channels.
abstract: The venom from spiders, scorpions, and sea anemone contain a rich diversity of protein toxins that interact with ion channel voltage sensors. Although atomic structures have been solved for many of these toxins, the surfaces that are critical for interacting with voltage sensors are poorly defined. Hanatoxin and SGTx are tarantula toxins that inhibit activation of K(v) channels by interacting with each of the four voltage sensors. In this study we set out to identify the active surface of these toxins by alanine-scanning SGTx and characterizing the interaction of each mutant with the K(v)2.1 channel. Examination of the concentration dependence for inhibition identified 15 mutants with little effect on the concentration dependence for toxin inhibition of the K(v)2.1 channel, and 11 mutants that display moderate to dramatic perturbations. Mapping of these results onto the structure of SGTx identifies one face of the toxin where mutations with pronounced perturbations cluster together, and a backside of the toxin where mutations are well tolerated. The active surface of SGTx contains a ring-like assembly of highly polar residues, with two basic residues that are particularly critical, concentrically arranged around a hydrophobic protrusion containing critical aliphatic and aromatic residues. These results identify the active surface of the toxin and reveal the types of side chains that are important for interacting with voltage sensors.
authors.affiliation: Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Wang
authors.forename: Soung Hun
authors.initials: SH
authors.lastname: Roh
authors.forename: Sunghwan
authors.initials: S
authors.lastname: Kim
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Lee
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Kenton J
authors.initials: KJ
authors.lastname: Swartz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D015640:Ion Channel Gating / Q000187:drug effects*; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051669:Shab Potassium Channels; D013111:Spider Venoms / Q000737:chemistry / Q000494:pharmacology*; D014981:Xenopus
chemical_list: D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; D013111:Spider Venoms