期刊
BIOCHEMISTRY
卷 51, 期 9, 页码 1862-1873出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi201633j
关键词
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资金
- Next-Generation BioGreen 21 Program [PJ008158]
- Rural Development Administration, Republic of Korea
- National Research Foundation of Korea
- Korean Government (MEST) [NRF-C1ABA001-2011-0018559]
- Brain Research Center [M103KV010005-06K2201-00610]
- BioImaging Research Center at the Gwangju Institute of Science and Technology
- Basic Research Projects in High-tech Industrial Technology
- Gwangju Institute of Science and Technology
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 Ca2+ 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 alpha-toxins and contained an alpha-helix, three beta-strands, and several turns stabilized by four disulfide bonds. This so-called cysteine-stabilized alpha-helix and beta-sheet (CS alpha beta) 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 a-toxins revealed that three regions [first long loop (Asp(8)-Ile(15)), beta-hairpin loop (Gly(39)-Leu(42)), and C-terminal segment (Arg(57)-Ala(63))] in kurtoxin significantly differ from the corresponding regions in scorpion alpha-toxins, suggesting that these regions may be important for interacting with Cav3 (T-type) Ca2+ 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 alpha-toxins. These distinct surface properties of kurtoxin could explain its binding to Cav3 (T-type) voltage-gated Ca2+ channels.
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