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利用从头转录组分析发现一种昆虫选择性钠通道调节剂。

De Novo Transcriptome Analysis of the Venom of with the Discovery of an Insect-Selective Na Channel Modulator.

机构信息

Program in Research and Development in Pharmaceuticals, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.

Toxicology and Pharmacology, Campus Gasthuisberg, University of Leuven (KU Leuven), 3000 Leuven, Belgium.

出版信息

Molecules. 2021 Dec 22;27(1):47. doi: 10.3390/molecules27010047.

DOI:10.3390/molecules27010047
PMID:35011282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8746590/
Abstract

The brown widow spider, , is a predator of a variety of agricultural insects and is also hazardous for humans. Its venom is a true pharmacopeia representing neurotoxic peptides targeting the ion channels and/or receptors of both vertebrates and invertebrates. The lack of transcriptomic information, however, limits our knowledge of the diversity of components present in its venom. The purpose of this study was two-fold: (1) carry out a transcriptomic analysis of the venom, and (2) investigate the bioactivity of the venom using an electrophysiological bioassay. From 32,505 assembled transcripts, 8 toxin families were classified, and the ankyrin repeats (ANK), agatoxin, centipede toxin, ctenitoxin, lycotoxin, scorpion toxin-like, and SCP families were reported in the venom gland. The diversity of venom was also uncovered by the transcriptomics approach with the presence of defensins, chitinases, translationally controlled tumor proteins (TCTPs), leucine-rich proteins, serine proteases, and other important venom components. The venom was also chromatographically purified, and the activity contained in the fractions was investigated using an electrophysiological bioassay with the use of a voltage clamp on ion channels in order to find if the neurotoxic effects of the spider venom could be linked to a particular molecular target. The findings show that U24-ctenitoxin-Pn1a involves the inhibition of the insect sodium (Na) channels, BgNa and DmNa. This study provides an overview of the molecular diversity of venom, which can be used as a reference for the venom of other spider species. The venom composition profile also increases our knowledge for the development of novel insecticides targeting voltage-gated sodium channels.

摘要

棕色寡妇蛛 ,是多种农业昆虫的捕食者,对人类也有危害。其毒液是一个真正的药典,包含针对脊椎动物和无脊椎动物的离子通道和/或受体的神经毒性肽。然而,缺乏转录组学信息限制了我们对其毒液中存在成分多样性的了解。本研究的目的有两个:(1)进行毒液的转录组分析;(2)使用电生理生物测定法研究毒液的生物活性。从 32505 条组装的转录本中,分类出 8 种毒素家族,在毒液腺中报告了锚蛋白重复(ANK)、芋螺毒素、蜈蚣毒素、栉齿刺尾鱼毒素、狼蛛毒素样、SCP 和 centipede 毒素家族。转录组学方法还揭示了毒液的多样性,存在防御素、几丁质酶、翻译控制肿瘤蛋白(TCTPs)、富含亮氨酸的蛋白、丝氨酸蛋白酶和其他重要的毒液成分。毒液也经过色谱纯化,并用电压钳在离子通道上进行电生理生物测定法研究包含在各个馏分中的活性,以确定蜘蛛毒液的神经毒性作用是否与特定的分子靶标有关。研究结果表明,U24-ctenitoxin-Pn1a 涉及昆虫钠离子(Na)通道 BgNa 和 DmNa 的抑制。本研究提供了 毒液分子多样性的概述,可作为其他蜘蛛物种毒液的参考。毒液成分谱也增加了我们对针对电压门控钠离子通道的新型杀虫剂开发的了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d1c/8746590/add3fbd4b1d4/molecules-27-00047-g011.jpg
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