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Biochemistry. 2012 Mar 6;51(9):1862-73. doi: 10.1021/bi201633j. Epub 2012 Feb 22.

Solution structure of kurtoxin: a gating modifier selective for Cav3 voltage-gated Ca(2+) channels.

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1
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.

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.

PMID:
22329781
PMCID:
PMC3295331
DOI:
10.1021/bi201633j
[Indexed for MEDLINE]
Free PMC Article
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