Department of Life Science, Trieste University, I-34127 Trieste, Italy.
Department of Science, Roma Tre University, I-00143 Rome, Italy.
Toxins (Basel). 2019 Feb 12;11(2):106. doi: 10.3390/toxins11020106.
Proteins of the ShK superfamily are characterized by a small conserved domain (ShKT), first discovered in small venom peptides produced by sea anemones, and acting as specific inhibitors of voltage-dependent and calcium-activated K⁺ channels. The ShK superfamily includes both small toxic peptides and larger multifunctional proteins with various functions. ShK toxins are often important components of animal venoms, where they perform different biological functions including neurotoxic and immunosuppressive effects. Given their high specificity and effectiveness, they are currently regarded as promising pharmacological lead compounds for the treatment of autoimmune diseases. Here, we report on the molecular analysis of ShKT domain containing proteins produced by the Mediterranean vampire snail , an ectoparasitic gastropod that feeds on benthic fishes. The high specificity of expression of most ShK transcripts in salivary glands identifies them as relevant components of venom. These ShK proteins display various structural architectures, being produced either as single-domain secretory peptides, or as larger proteins combining the ShKT with M12 or CAP domains. Both ShKT-containing genes and their internal ShKT domains undergo frequent duplication events in , ensuring a high level of variability that is likely to play a role in increasing the range of their potential molecular targets.
ShK 超家族的蛋白质的特征是一个小的保守结构域（ShKT），最初在海葵产生的小毒液肽中发现，作为电压依赖性和钙激活的 K ⁺ 通道的特异性抑制剂。ShK 超家族包括小的毒性肽和具有各种功能的更大的多功能蛋白质。ShK 毒素通常是动物毒液的重要组成部分，在毒液中具有不同的生物学功能，包括神经毒性和免疫抑制作用。鉴于它们的高特异性和有效性，它们目前被认为是治疗自身免疫性疾病的有前途的药理学先导化合物。在这里，我们报告了由地中海吸血蜗牛产生的含有 ShKT 结构域的蛋白质的分子分析，地中海吸血蜗牛是一种寄生在海底鱼类上的外寄生虫腹足纲动物。大多数 ShK 转录物在唾液腺中的高特异性表达将它们鉴定为毒液的相关成分。这些 ShK 蛋白显示出各种结构架构，要么作为单一结构域的分泌肽产生，要么作为更大的蛋白质，将 ShKT 与 M12 或 CAP 结构域结合。含有 ShKT 的基因及其内部 ShKT 结构域在 中经常发生重复事件，确保了高水平的可变性，这可能在增加它们潜在分子靶标的范围方面发挥作用。
