Conkunitzin-S1 is the first member of a new Kunitz-type neurotoxin family. Structural and functional characterization.
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.
Bayrhuber
Monika
M
Department for NMR-based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Vijayan
Vinesh
V
Ferber
Michael
M
Graf
Roland
R
Korukottu
Jegannath
J
Imperial
Julita
J
Garrett
James E
JE
Olivera
Baldomero M
BM
Terlau
Heinrich
H
Zweckstetter
Markus
M
Becker
Stefan
S
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
D008978:Mollusk Venoms; D009498:Neurotoxins; C504068:conkunitzin-S1, Conus striatus