| 长孙东亭,朱晓鹏,吴勇,等.αB-芋螺毒素VxXXIVA与α9α10乙酰胆碱受体结合特性的研究[J].中国海洋药物,2015,34(5):47-53. |
| αB-芋螺毒素VxXXIVA与α9α10乙酰胆碱受体结合特性的研究 |
| Binding Characteristics of αB-Conotoxin VxXXIVA#$NBSon α9α10 Nicotinic Acetylcholine Receptor |
| 投稿时间：2015-03-28 修订日期：2015-07-08 |
| DOI： |
| 中文关键词: αB -芋螺毒素VxXXIVA,α9α10S乙酰胆碱受体,结合位点,电压依赖性研究。 |
| English Keywords:S αB-conotoxin VxXXIVA, α9α10 nAChR, Binding site, Voltage dependence assay. |
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| 中文摘要: |
| αB-芋螺毒素VxXXIVA（αB-VxXXIVA）是我们从海南产菖蒲芋螺（Conus vexillum）中发现的一个新超家族毒素肽，是α9α10乙酰胆碱受体（nAChR）亚型的特异阻断剂。αB-VxXXIVA仅含有简单的4个半胱氨酸模式（C1-C2C3-C4），其活性最强异构体的二硫键连接方式是Cys1-Cys2和 Cys3-Cys4。存在于外周神经系统中的α9α10 nAChR是治疗神经痛、癌症化疗、乳腺癌和肺癌的新靶点，具有很重要的临床意义。具有独特结构的αB-VxXXIVA与α9α10 nAChR之间的结合特性尚不清楚。为此，本文对αB-VxXXIVA与α9α10 nAChR受体之间的结合位点和电压依赖性进行了研究。发现它与具有竞争性结合特性的α-芋螺毒素的结合位点有部分重叠，但又完全不相同，是一个新的微位点，其结合活性随膜电压的升高而不会改变，不具有电压依赖性。该研究结果将为αB- VxXXIVA作为工具药开发、α9α10 nAChR受体结构与功能的研究、以及基于该受体为药靶的药物设计提供理论基础。 |
| English Summary: |
| αB-conotoxin VxXXIVA (αB-VxXXIVA) is a novel inhibitor of α9α10 nicotinic acetylcholine receptor (nAChR) from Conus vexillum native to Hainan, which delineates a new conotoxin superfamily B. The αB-VxXXIVA contains a simple 4-Cysteine framwork (C1-C2C3-C4). The most potent isomer of αB-VxXXIVA is that has Cys1-Cys2 and Cys3-Cys4 disulfide bonds. The α9α10 nAChR subtype exists peripheral nervous system, which is the target of neuropathic pain, cancer chemotherapy, lung and breast cancers and is also of increasing interest in biomedicine. Binding characteristics of unique structural αB-VxXXIVA to α9α10 nAChR remains unknown. Here we explored the binding properties between αB-VxXXIVA and α9α10 nAChR, as well as its voltage dependence assay. αB-VxXXIVA had partial overlapping binding sites on the α9α10 nAChR with α-conotoxins, but partial different from the ACh-binding site where α-conotoxins generally bind competitively, which is a new microsite. The membrane hold voltage variation did not change the activity of αB-VxXXIVA blocking α9α10 nAChR, which meant block by αB-VxXXIVA was not voltage dependent. The results shown here would be valuable for developing αB-VxXXIVA as research tool, structure/function research of α9α10 nAChR subtype, and designing new drug leads. |
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