General mechanism of spider toxin family I acting on sodium channel Nav1.7.
General mechanism of spider toxin family I acting on sodium channel Nav1.7.
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DOI：
10.24272/j.issn.2095-8137.2022.185
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发表时间：
2022-09-18
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
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作者：
动物毒液中的各种肽毒素抑制电压门控钠离子通道Nav1.7，包括Nav-targeting spider toxin（NaSpTx）Family I。NaSpTx家族I中的毒素具有相似的结构，即，N-末端、1-4环和C-末端。在这里，我们使用Mu-theraphotoxin-Ca 2a（Ca 2a），一种从Cyriopagopus albostriatus中分离的肽，作为模板来研究NaSpTx家族I中毒素的一般性质。毒素在通过类似的疏水残基与Nav1.7结合之前与细胞膜相互作用。第1环、第4环和C端的残基主要与结构域II的S3-S4接头相互作用，尤其是与E818结合的碱性氨基酸。我们还确定了环2在Ca 2a中关于其与Nav1.7的亲和力的关键作用。我们的研究结果提供了进一步的证据表明，NaSpTx家族I毒素与Nav1.7具有相似的结构和结合机制。
Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin (NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.e., N-terminal, loops 1–4, and C-terminal. Here, we used Mu-theraphotoxin-Ca2a (Ca2a), a peptide isolated from Cyriopagopus albostriatus, as a template to investigate the general properties of toxins in NaSpTx Family I. The toxins interacted with the cell membrane prior to binding to Nav1.7 via similar hydrophobic residues. Residues in loop 1, loop 4, and the C-terminal primarily interacted with the S3–S4 linker of domain II, especially basic amino acids binding to E818. We also identified the critical role of loop 2 in Ca2a regarding its affinity to Nav1.7. Our results provide further evidence that NaSpTx Family I toxins share similar structures and mechanisms of binding to Nav1.7.
蜈蚣毒素SsTx-4抑制内向整流钾通道的分子机制
DOI：
10.1016/j.jbc.2021.101076
发表时间：
2021-09
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Tang D;Xu J;Li Y;Zhao P;Kong X;Hu H;Liang S;Tang C;Liu Z
通讯作者：
Liu Z