Kryukova Elena V, Vulfius Catherine A, Ziganshin Rustam H, Andreeva Tatyana V, Starkov Vladislav G, Tsetlin Victor I, Utkin Yuri N
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
Institute of Cell Biophysics Russian Academy of Sciences, 3 Institutskaya Street, Pushchino Moscow region, 142290, Russia.
J Venom Res. 2020 Jul 6;10:23-29. eCollection 2020.
Venoms of viperid snakes affect mostly hemostasis, while C-type lectin-like proteins (CTLPs), one of the main components of viperid venoms, act as anticoagulants, procoagulants, or agonists/antagonists of platelet activation. However, we have shown earlier that CTLPs from the saw-scaled viper , called emunarecins EM1 and EM2, were able to inhibit nicotinic acetylcholine receptors (nAChRs) in neurons of a pond snail (). Here we analysed the structure of the emunarecins by mass spectrometry and report that EM1 and EM2 inhibit fluorescent α-bungarotoxin binding to both muscle-type nAChRs from and human neuronal α7 nAChRs. EM1 at 23µM and EM2 at 9µM almost completely prevented fluorecsent α-bungarotoxin binding to muscle-type nAChRs. Interaction with human neuronal α7 nAChR was weaker; EM1 at the concentration of 23µM blocked the α-bungarotoxin binding only by about 40% and EM2 at 9µM by about 20%. The efficiency of the EM2 interaction with nAChRs was comparable to that of a non-conventional toxin, WTX, from cobra venom. Together with the data obtained earlier, these results show that CTLPs may represent new nAChR ligands.
蝰蛇科蛇类的毒液主要影响止血功能，而作为蝰蛇科蛇类毒液主要成分之一的C型凝集素样蛋白（CTLPs），可作为抗凝剂、促凝剂或血小板激活的激动剂/拮抗剂。然而，我们之前已经表明，锯鳞蝰蛇的CTLPs，即伊穆纳菌素EM1和EM2，能够抑制池塘蜗牛神经元中的烟碱型乙酰胆碱受体（nAChRs）。在此，我们通过质谱分析了伊穆纳菌素的结构，并报告称EM1和EM2抑制荧光α-银环蛇毒素与来自[具体物种]的肌肉型nAChRs以及人类神经元α7 nAChRs的结合。23µM的EM1和9µM的EM2几乎完全阻止了荧光α-银环蛇毒素与肌肉型nAChRs的结合。与人类神经元α7 nAChR的相互作用较弱；23µM浓度的EM1仅阻断约40%的α-银环蛇毒素结合，9µM浓度的EM2阻断约20%。EM2与nAChRs相互作用的效率与眼镜蛇毒液中一种非常规毒素WTX相当。结合之前获得的数据，这些结果表明CTLPs可能代表新的nAChR配体。
