TxXIIIA, an atypical homodimeric conotoxin found in the Conus textile venom
TxXIIIA, an atypical homodimeric conotoxin found in the Conus textile venom
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DOI：
10.1016/j.jprot.2009.01.021
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发表时间：
2009-03-06
影响因子：
3.3
通讯作者：
De Pauw, Edwin
中科院分区：
文献类型：
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作者：
Quinton, Loic;Gilles, Nicolas;De Pauw, Edwin
肉食性芋螺的毒液由数百种肽毒素组成。其中许多肽对特定的膜受体（例如离子通道或G蛋白偶联受体）表现出高选择性。这种特性使它们成为研究受体和潜在新药的非常有前途的工具。芋螺毒素的合成有不同的折叠，每一折叠都与特定的药理活性有关。为了发现新的芋螺毒素，我们采用离线LC-MALDI-TOF/TOF质谱技术，从织锦芋螺毒液中寻找具有原始折叠结构的毒素。在二硫键的“溶液中”还原之前和之后，通过MALDI-TOF（在2，5-二羟基苯甲酸中）分析毒液级分。光谱的比较允许大量的芋螺毒素根据二硫键的数量进行分类。我们重点关注m/z 2785.7（非还原）/ 1398.4（还原）的组分，其可能代表一种新型的同源二聚体毒素。序列TSDCCFYHNCCC通过还原物质的从头测序确定，并代表新的折叠。该序列已经被描述为芋螺毒素支架IX前体（expasy：Q9 BPH 1）的C-末端部分，但是我们的研究的力量在于质谱法突出了毒素的正确长度以及其同二聚体形式，这不能通过先前的cDNA研究确定。TxXIIIA也是第一个具有五个二硫键的同源二聚体芋螺毒素，并且由含有奇数个半胱氨酸的两个单体组成。(c)2009爱思唯尔有限公司版权所有。
Venoms of predatory Conus snails are composed of several hundreds of peptide toxins. Many of these peptides display a high selectivity for particular membrane receptors such as ionic channels or G-protein coupled receptors. This property makes them very promising tools for the study of receptors and potential new drugs. Conus snails synthesize toxins under various folds, each fold related to particular pharmacological activities. Aiming the discovery of new conotoxins, we looked for toxins with original fold in the Conus textile venom by offline LC-MALDI-TOF/TOF mass spectrometry. Venom fractions were analysed by MALDI-TOF (in 2,5-dihydroxybenzoic acid) before and after the "in-solution" reduction of the disulfide bridges. Comparison of the spectra allows the classification of a large number of conotoxins according to the number of disulfide bridges. We focussed on a component at m/z 2785.7 (non-reduced)/ 1398.4 (reduced), which might represent a novel type of homodimeric toxin. The sequence TSDCCFYHNCCC was determined by De novo sequencing on the reduced species and represent a new fold. This sequence has already been described as the C-terminus part of a conotoxin scaffold IX precursor (expasy: Q9BPH1) but the power of our study resides in the fact that mass spectrometry highlights the right length of the toxin as well as its homodimeric form which could not be determined by the previous cDNA study. TxXIIIA is also the first homodimeric conotoxin with five disulfide bonds and composed of two monomers containing an odd number of cysteins. (c) 2009 Elsevier B.V. All rights reserved.