Solution Structure and Functional Characterization of Jingzhaotoxin-XI: A Novel Gating Modifier of both Potassium and Sodium Channels

详细信息    查看全文

• 作者：Zhi Liao ; Chunhua Yuan ; Meichun Deng ; Jiang Li ; Jinjun Chen ; Yuejun Yang ; Weijun Hu ; Songping Liang
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：December 26, 2006
• 年：2006
• 卷：45
• 期：51
• 页码：15591 - 15600
• 全文大小：443K
• 年卷期：v.45,no.51(December 26, 2006)
• ISSN：1520-4995

文摘

JZTX-XI is a peptide toxin isolated from the venom of the Chinese spider Chilobrachysjingzhao. It contains 34 residues including six cysteine residues with disulfide bridges linked in the patternof I-IV, II-V, and III-VI. Using 3'- and 5'-RACE methods, the full-length cDNA was identified asencoding an 86-residue precursor of JZTX-XI. In the electrophysiological assay, JZTX-XI shows activitytoward the Kv2.1 channel in a way similar to hanatoxin1 and SGTx1 that both the activation and thedeactivation processes are affected, which is in accordance with the high sequence homology amongthem (over 60% identity). On the other hand, JZTX-XI also exhibits specific interaction against the Navchannels of rat cardiac myocytes with a significant reduction in the peak current and slowing of channelinactivation. The solution structure of native JZTX-XI was determined by ¹H NMR methods to identifythe structural basis of these specific activities. Structural comparison of JZTX-XI with other gating modifiertoxins shows that they all adopt a similar surface profile, a hydrophobic patch surrounded by chargedresidues such as Arg or Lys, which might be a common structural factor responsible for toxin-channelinteraction. JZTX-XI might be an ideal tool to further investigate how spider toxins recognize various ionchannels as their targets.