Three-dimensional solution structure of the sodium channel agonist/antagonist δ-conotoxin TxVIA
Three-dimensional solution structure of the sodium channel agonist/antagonist δ-conotoxin TxVIA
复制标题
DOI：
10.1074/jbc.m206833200
复制
发表时间：
2002-09-27
影响因子：
4.8
通讯作者：
Sato, K
中科院分区：
文献类型：
--
作者：
Kohno, T;Sasaki, T;Sato, K
采用二维H-1 NMR模拟退火计算，确定了27聚肽钠通道激动剂/拮抗剂delta-conotoxin TxVIX的三维溶液结构。基于核Overhauser效应连接得到的360个距离约束、28个扭转角约束、27个氢键和二硫键约束，得到了delta- concontoxin TxVIA的共20个收敛结构。主链原子（N, C- α， C）的平均座标位置的原子均方根差为0.35 +/- 0.07埃，整个肽中所有重原子的平均座标位置的原子均方根差为0.98 +/- 0.14埃。delta- concontoxin TxVIA的分子结构是由一个短的三链反平行β -片组成。整个β -薄片的拓扑结构为+2x， -1，这与其他concontoxins相同。然而，delta- concontoxin TxVIIA的三维结构在分子的一侧有一个不寻常的疏水斑块，这可能在钠通道结合中起重要作用。这些结果为理解钠离子通道通过毒素-通道相互作用调控的机制以及了解不同离子通道的区别提供了分子基础。
The three-dimensional solution structure of delta-conotoxin TxVIX a 27-mer peptide agonist/antagonist of sodium channels, was determined by two-dimensional H-1 NMR spectroscopy with simulated annealing calculations. A total of 20 converged structures of delta-conotoxin TxVIA were obtained on the basis of 360 distance constraints obtained from nuclear Overhauser effect connectivities, 28 torsion angle constraints, and 27 constraints associated with hydrogen bonds and disulfide bonds. The atomic root mean square difference about the averaged coordinate positions is 0.35 +/- 0.07 Angstrom for the backbone atoms (N, C-alpha, C) and 0.98 +/- 0.14 Angstrom for all heavy atoms of the entire peptide. The molecular structure of delta-conotoxin TxVIA is composed of a short triple-stranded antiparallel beta-sheet. The overall beta-sheet topology is +2x, -1, which is the same as those for other conotoxins. However, the three-dimensional structure of delta-conotoxin TxVIIA has an unusual hydrophobic patch on one side of the molecule, which may play an important role in the sodium channel binding. These results provide a molecular basis for understanding the mechanism of sodium channel modulation through the toxin-channel interaction and insight into the discrimination of different ion channels.