Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str. 16/10, Moscow 117997, Russian Federation.
Trends Pharmacol Sci. 2015 Feb;36(2):109-23. doi: 10.1016/j.tips.2014.11.003. Epub 2014 Dec 17.
Snake venom neurotoxins and lymphocyte antigen 6 (Ly6) proteins, most of the latter being membrane tethered by a glycosylphosphatidylinositol (GPI) anchor, have a variety of biological activities, but their three-finger (3F) folding combines them in one Ly6/neurotoxin family. Subsets of two groups, represented by α-neurotoxins and Lynx1, respectively, interact with nicotinic acetylcholine receptors (nAChR) and, hence, are of therapeutic interest for the treatment of neurodegenerative diseases, pain, and cancer. Information on the mechanisms of action and 3D structure of the binding sites, which is required for drug design, is available from the 3D structure of α-neurotoxin complexes with nAChR models. Here, I compare the structural and functional features of α-neurotoxins versus Lynx1 and its homologs to get a clearer picture of Lynx1-nAChR interactions that is necessary for fundamental science and practical applications.
蛇毒神经毒素和淋巴细胞抗原 6（Ly6）蛋白，后者大多数通过糖基磷脂酰肌醇（GPI）锚定连接到细胞膜上，具有多种生物学活性，但它们的三指（3F）折叠将它们组合到一个 Ly6/神经毒素家族中。以α-神经毒素和 Lynx1 为代表的两组亚群分别与烟碱型乙酰胆碱受体（nAChR）相互作用，因此对于治疗神经退行性疾病、疼痛和癌症具有治疗意义。作用机制和结合位点的 3D 结构的信息对于药物设计是必需的，这些信息可以从α-神经毒素与 nAChR 模型的复合物的 3D 结构中获得。在这里，我比较了α-神经毒素与 Lynx1 及其同源物的结构和功能特征，以更清楚地了解 Lynx1-nAChR 相互作用，这对于基础科学和实际应用都是必要的。
