title: Conkunitzin-S1 is the first member of a new Kunitz-type neurotoxin family. Structural and functional characterization.
abstract: Conkunitzin-S1 (Conk-S1) is a 60-residue neurotoxin from the venom of the cone snail Conus striatus that interacts with voltage-gated potassium channels. Conk-S1 shares sequence homology with Kunitz-type proteins but contains only two out of the three highly conserved cysteine bridges, which are typically found in these small, basic protein modules. In this study the three-dimensional structure of Conk-S1 has been solved by multidimensional NMR spectroscopy. The solution structure of recombinant Conk-S1 shows that a Kunitz fold is present, even though one of the highly conserved disulfide cross-links is missing. Introduction of a third, homologous disulfide bond into Conk-S1 results in a functional toxin with similar affinity for Shaker potassium channels. The affinity of Conk-S1 can be enhanced by a pore mutation within the Shaker channel pore indicating an interaction of Conk-S1 with the vestibule of potassium channels.
authors.affiliation: Department for NMR-based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Bayrhuber
authors.forename: Vinesh
authors.initials: V
authors.lastname: Vijayan
authors.forename: Michael
authors.initials: M
authors.lastname: Ferber
authors.forename: Roland
authors.initials: R
authors.lastname: Graf
authors.forename: Jegannath
authors.initials: J
authors.lastname: Korukottu
authors.forename: Julita
authors.initials: J
authors.lastname: Imperial
authors.forename: James E
authors.initials: JE
authors.lastname: Garrett
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
authors.forename: Heinrich
authors.initials: H
authors.lastname: Terlau
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
mesh_terms: D000595:Amino Acid Sequence; D004926:Escherichia coli / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D009498:Neurotoxins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D008978:Mollusk Venoms; D009498:Neurotoxins; C504068:conkunitzin-S1, Conus striatus