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 ?-toxins and contained an ?-helix, three ?-strands, and several turns stabilized by four disulfide bonds. This so-called "cysteine-stabilized ?-helix and ?-sheet (CS??)" 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 ?-toxins revealed that three regions [first long loop (Asp(8)-Ile(15)), ?-hairpin loop (Gly(39)-Leu(42)), and C-terminal segment (Arg(57)-Ala(63))] in kurtoxin significantly differ from the corresponding regions in scorpion ?-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 ?-toxins. These distinct surface properties of kurtoxin could explain its binding to Cav3 (T-type) voltage-gated Ca(2+) channels.

SUBMITTER: Lee CW 

PROVIDER: S-EPMC3295331 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature