Solution Structure of Kurtoxin: A Gating Modifier Selective for Cav3 Voltage-Gated Ca2+ Channels
| Autor: | Chanhyung Bae, Chul Won Lee, Jae Ha Ryu, Jae Il Kim, Ha Hyung Kim, Jaeho Lee, Kenton J. Swartz, Toshiyuki Kohno |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Protein Conformation Stereochemistry Scorpion Venoms Gating Crystallography X-Ray Biochemistry Protein Structure Secondary Article chemistry.chemical_compound Protein structure Animals Voltage-dependent calcium channel biology Voltage-gated ion channel Nuclear magnetic resonance spectroscopy Parabuthus transvaalicus biology.organism_classification Solutions chemistry Kurtoxin Calcium Channels Peptides Ion Channel Gating |
| Zdroj: | Biochemistry |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi201633j |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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