Characterization of an α 4/7-Conotoxin LvIF from Conus lividus That Selectively Blocks α3β2 Nicotinic Acetylcholine Receptor.
Characterization of an α 4/7-Conotoxin LvIF from Conus lividus That Selectively Blocks α3β2 Nicotinic Acetylcholine Receptor.
复制标题
来自青花芋螺的 α 4/7-芋螺毒素 LvIF 的表征，该毒素选择性阻断 α 3 β 2 烟碱乙酰胆碱受体
DOI：
10.3390/md19070398
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发表时间：
2021-07-17
期刊：
影响因子：
5.4
通讯作者：
Luo S
中科院分区：
文献类型：
--
作者：
Guo M;Yu J;Zhu X;Zhangsun D;Luo S
烟碱型乙酰胆碱受体（nAChR）是由5个亚基组成的五聚体配体门控离子通道跨膜蛋白，广泛分布于中枢和外周神经系统。nAChR与各种神经系统疾病相关，包括精神分裂症、阿尔茨海默病、帕金森病、癫痫和神经痛。含有α3亚基的受体与镇痛有关，这引起了我们对它们在药理学研究中的作用的兴趣。本研究从青芋螺（Conus lividus，C. lividus）。采用两步氧化法合成了具有天然结构的成熟LvIF。双电极电压钳法检测α-CTx lvIF对nAChR的阻断作用。结果表明，α-CTx LvIF对非洲爪蟾卵母细胞表达的r α 3 β 2和r α 6/α 3 β 2 β 3 nAChR亚型有较强的抑制作用，其半数抑制浓度（IC 50）分别为8.9 nM和14.4 nM。α-CTx LvIF对其他nAChR亚型无明显抑制作用。同时，我们还进行了α-CTxs MII与LvIF的竞争结合实验，结果表明α-CTxs LvIF和MII与rα3β2 nAChR在部分重叠区域结合。这些结果表明，α-CTx LvIF有望成为研究rα3β2 nAChR相关神经生理学和药理学的新工具。
Nicotinic acetylcholine receptor (nAChR), a member of pentameric ligand-gated ion channel transmembrane protein composed of five subunits, is widely distributed in the central and peripheral nervous system. The nAChRs are associated with various neurological diseases, including schizophrenia, Alzheimer’s disease, Parkinson’s disease, epilepsy and neuralgia. Receptors containing the α3 subunit are associated with analgesia, generating our interest in their role in pharmacological studies. In this study, α-conotoxin (α-CTx) LvIF was identified as a 16 amino acid peptide using a genomic DNA clone of Conus lividus (C. lividus). The mature LvIF with natural structure was synthesized by a two-step oxidation method. The blocking potency of α-CTx lvIF on nAChR was detected by a two-electrode voltage clamp. Our results showed that α-CTx LvIF was highly potent against rα3β2 and rα6/α3β2β3 nAChR subtypes, The half-maximal inhibitory concentration (IC50) values of α-CTx LvIF against rα3β2 and rα6/α3β2β3 nAChRs expressed in Xenopus oocytes were 8.9 nM and 14.4 nM, respectively. Furthermore, α-CTx LvIF exhibited no obvious inhibition on other nAChR subtypes. Meanwhile, we also conducted a competitive binding experiment between α-CTxs MII and LvIF, which showed that α-CTxs LvIF and MII bind with rα3β2 nAChR at the partial overlapping domain. These results indicate that the α-CTx LvIF has high potential as a new candidate tool for the studying of rα3β2 nAChR related neurophysiology and pharmacology.
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从 α-芋螺毒素 GIC 与 Ac-AChBP 复合物的晶体结构到其对 α3β2 nAChR 高选择性的分子决定因素。
影响因子：
4.6
作者：
Lin B;Xu M;Zhu X;Wu Y;Liu X;Zhangsun D;Hu Y;Xiang SH;Kasheverov IE;Tsetlin VI;Wang X;Luo S
通讯作者：
Luo S
影响因子：
3.6
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
4.8
作者：
Luo, Sulan;Zhangsun, Dongting;Whiteaker, Paul
通讯作者：
Whiteaker, Paul
影响因子：
3.6
作者：
Hone, Arik J.;McIntosh, J. Michael;Albillos, Almudena
通讯作者：
Albillos, Almudena