肩突硬蜱（Ixodes scapularis）又称黑足蜱（blacklegged tick），是广泛分布、相当危险的吸血生物，硬蜱可以传播很多疾病，包括臭名昭著的莱姆病。它产生的毒液中含有大量的神经多肽毒素，可特异性作用于宿主离子通道，使宿主无法感受疼痛，从而不易被察觉。

近日，中国科学院昆明植物研究所胡凯锋研究组和中国科学院昆明动物研究所赖仞研究组合作，从肩突硬蜱唾液腺中分离出一种新的多肽神经毒素ISTX-I，此神经毒素特异性地抑制钠离子通道Nav1.7，对其他钠离子通道亚型没有任何影响。通过大肠杆菌体外表达纯化ISTX-I多肽神经毒素，实验验证其二硫键的配对方式，体外膜片钳实验验证体外表达的ISTX-I多肽毒素的功能。应用核磁共振NMR技术对ISTX-I多肽的空间三维结构进行解析，结果显示：尽管ISTX-I具有与ICK结构一样的二硫键配对方式（C1-C4,C2-C5,C3-C6），但是ISTX-I多肽展示了一种新的结构折叠模式，与其他多肽毒素常规DDH或者ICK结构模式明显不同；通过钠离子通道毒素的序列系统进化分析，进一步支持ISTX-I毒素与蜘蛛毒素进化上更相近的论点。

该研究成果以A sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin folds 为题在《科学报告》（Scientific Reports)发表。容明强、刘将新和张美玲为该文的共同第一作者。该项目得到了国家自然科学基金（31400642，31260208等）、云南省应用基础研究计划（2011FB132，2015FB170等）、中科院“西部之光”等基金资助。

ISTX-I多肽毒素新颖的三维结构以及与毒素标准结构模式DDH和ICK的区别

原文摘要：

A sodium channel inhibitor ISTX-I with a novel structure provides a new hint at the evolutionary link between two toxin folds

Members of arachnida, such as spiders and scorpions, commonly produce venom with specialized venom glands, paralyzing their prey with neurotoxins that specifically target ion channels. Two well-studied motifs, the disulfide-directed hairpin (DDH) and the inhibitor cystine knot motif (ICK), are both found in scorpion and spider toxins. As arachnids, ticks inject a neurotoxin-containing cocktail from their salivary glands into the host to acquire a blood meal, but peptide toxins acting on ion channels have not been observed in ticks. Here, a new neurotoxin (ISTX-I) that acts on sodium channels was identified from the hard tick Ixodes scapularis and characterized. ISTX-I exhibits a potent inhibitory function with an IC50 of 1.6 μM for sodium channel Nav1.7 but not other sodium channel subtypes. ISTX-I adopts a novel structural fold and is distinct from the canonical ICK motif. Analysis of the ISTX-I, DDH and ICK motifs reveals that the new ISTX-I motif might be an intermediate scaffold between DDH and ICK, and ISTX-I is a clue to the evolutionary link between the DDH and ICK motifs. These results provide a glimpse into the convergent evolution of neurotoxins from predatory and blood-sucking arthropods.