PDF(Pubmed)
Abstract：
This review covers briefly the work carried out at our institute (IBCh), in many cases in collaboration with other Russian and foreign laboratories, for the last 50 years. It discusses the discoveries and studies of various animal toxins, including protein and peptide neurotoxins acting on the nicotinic acetylcholine receptors (nAChRs) and on other ion channels. Among the achievements are the determination of the primary structures of the α-bungarotoxin-like three-finger toxins (TFTs), covalently bound dimeric TFTs, glycosylated cytotoxin, inhibitory cystine knot toxins (ICK), modular ICKs, and such giant molecules as latrotoxins and peptide neurotoxins from the snake, as well as from other animal venoms. For a number of toxins, spatial structures were determined, mostly by 1H-NMR spectroscopy. Using this method in combination with molecular modeling, the molecular mechanisms of the interactions of several toxins with lipid membranes were established. In more detail are presented the results of recent years, among which are the discovery of α-bungarotoxin analogs distinguishing the two binding sites in the muscle-type nAChR, long-chain α-neurotoxins interacting with α9α10 nAChRs and with GABA-A receptors, and the strong antiviral effects of dimeric phospholipases A2. A summary of the toxins obtained from arthropod venoms includes only highly cited works describing the molecules\' success story, which is associated with IBCh. In marine animals, versatile toxins in terms of structure and molecular targets were discovered, and careful work on α-conotoxins differing in specificity for individual nAChR subtypes gave information about their binding sites.
摘要：
这篇综述简要介绍了我们研究所(IBCh)开展的工作，在许多情况下，与其他俄罗斯和外国实验室合作，在过去的50年里.它讨论了各种动物毒素的发现和研究，包括作用于烟碱乙酰胆碱受体（nAChRs）和其他离子通道的蛋白质和肽神经毒素。成就之一是确定α-银环蛇毒素样三指毒素（TFT）的一级结构，共价结合的二聚体TFT，糖基化细胞毒素，抑制性胱氨酸结毒素（ICK），模块化ICKs,和巨大的分子，如蛇毒素和肽神经毒素，以及其他动物毒液。对于一些毒素，确定了空间结构，主要通过1H-NMR光谱。使用这种方法与分子建模相结合，建立了几种毒素与脂质膜相互作用的分子机制。更详细地介绍了近年来的结果，其中发现了区分肌肉型nAChR中两个结合位点的α-银环蛇毒素类似物，长链α-神经毒素与α9α10nAChRs和GABA-A受体相互作用，以及二聚磷脂酶A2的强大抗病毒作用。从节肢动物毒液中获得的毒素的摘要仅包括描述分子成功故事的高度引用的作品，与IBCh相关。在海洋动物中，发现了结构和分子靶标方面的多种毒素，对单个nAChR亚型的特异性不同的α-芋螺毒素的仔细研究提供了有关其结合位点的信息。
