A Recurrent Motif: Diversity and Evolution of ShKT Domain Containing Proteins in the Vampire Snail Cumia reticulata
A Recurrent Motif: Diversity and Evolution of ShKT Domain Containing Proteins in the Vampire Snail Cumia reticulata
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DOI：
10.3390/toxins11020106
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发表时间：
2019-02-01
期刊：
影响因子：
4.2
通讯作者：
Modica, Maria Vittoria
中科院分区：
文献类型：
--
作者：
Gerdol, Marco;Cervelli, Manuela;Modica, Maria Vittoria
ShK 超家族蛋白的特点是有一个小的保守结构域 (ShKT)，该结构域首先在海葵产生的小毒液肽中发现，可作为电压依赖性和钙激活 K+ 通道的特异性抑制剂。 ShK超家族包括小的有毒肽和具有多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成分，发挥不同的生物学功能，包括神经毒性和免疫抑制作用。鉴于其高度特异性和有效性，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，我们报告了对地中海吸血蜗牛 Cumia reticulata（一种以底栖鱼类为食的外寄生腹足动物）产生的含有 ShKT 结构域的蛋白质的分子分析。大多数 ShK 转录本在唾液腺中表达的高度特异性，将它们识别为网纹蝽毒液的相关成分。这些 ShK 蛋白表现出不同的结构体系，可以作为单域分泌肽产生，也可以作为将 ShKT 与 M12 或 CAP 域结合的较大蛋白质产生。含有 ShKT 的基因及其内部 ShKT 结构域在 C. reticulata 中经历频繁的重复事件，确保了高水平的变异性，这可能在增加其潜在分子靶标的范围方面发挥作用。
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 Cumia reticulata, 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 C. reticulata 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 C. reticulata, ensuring a high level of variability that is likely to play a role in increasing the range of their potential molecular targets.