title: Solution structure of kurtoxin: a gating modifier selective for Cav3 voltage-gated Ca(2+) channels.
abstract: Kurtoxin is a 63-amino acid polypeptide isolated from the venom of the South African scorpion Parabuthus transvaalicus. It is the first and only peptide ligand known to interact with Cav3 (T-type) voltage-gated Ca(2+) channels with high affinity and to modify the voltage-dependent gating of these channels. Here we describe the nuclear magnetic resonance (NMR) solution structure of kurtoxin determined using two- and three-dimensional NMR spectroscopy with dynamical simulated annealing calculations. The molecular structure of the toxin was highly similar to those of scorpion α-toxins and contained an α-helix, three β-strands, and several turns stabilized by four disulfide bonds. This so-called "cysteine-stabilized α-helix and β-sheet (CSαβ)" motif is found in a number of functionally varied small proteins. A detailed comparison of the backbone structure of kurtoxin with those of the scorpion α-toxins revealed that three regions [first long loop (Asp(8)-Ile(15)), β-hairpin loop (Gly(39)-Leu(42)), and C-terminal segment (Arg(57)-Ala(63))] in kurtoxin significantly differ from the corresponding regions in scorpion α-toxins, suggesting that these regions may be important for interacting with Cav3 (T-type) Ca(2+) channels. In addition, the surface profile of kurtoxin shows a larger and more focused electropositive patch along with a larger hydrophobic surface compared to those seen on scorpion α-toxins. These distinct surface properties of kurtoxin could explain its binding to Cav3 (T-type) voltage-gated Ca(2+) channels.
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Lee
authors.forename: Chanhyung
authors.initials: C
authors.lastname: Bae
authors.forename: Jaeho
authors.initials: J
authors.lastname: Lee
authors.forename: Jae Ha
authors.initials: JH
authors.lastname: Ryu
authors.forename: Ha Hyung
authors.initials: HH
authors.lastname: Kim
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kohno
authors.forename: Kenton J
authors.initials: KJ
authors.lastname: Swartz
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Kim
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D015640:Ion Channel Gating; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012604:Scorpion Venoms / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions
chemical_list: D015220:Calcium Channels; D010455:Peptides; D012604:Scorpion Venoms; D012996:Solutions; C118444:kurtoxin