Specialisation of the Venom Gland Proteome in Predatory Cone Snails Reveals Functional Diversification of the Conotoxin Biosynthetic Pathway
Specialisation of the Venom Gland Proteome in Predatory Cone Snails Reveals Functional Diversification of the Conotoxin Biosynthetic Pathway
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DOI：
10.1021/pr1012976
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发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Purcell, Anthony W.
中科院分区：
文献类型：
--
作者：
Safavi-Hemami, Helena;Siero, William A.;Purcell, Anthony W.
芋螺毒素是一种来自海洋螺类的毒素肽，随着物种形成而迅速多样化。每个物种可以合成1000到1900种不同的毒素，物种间几乎没有重叠。芋螺毒素表现出前所未有的翻译后修饰程度，最常见的是二硫键的形成。尽管结构复杂的肽的多样性很大，很少有人知道的腺体蛋白负责其生物合成和成熟。在这里，蛋白质组学的芋螺毒腺的审讯导致了新的腺蛋白的毒素合成和分泌的潜在重要性的鉴定。共161和157蛋白质和蛋白质异构体的毒液腺的新奥霍兰芋螺和Corms victoriae，分别确定。毒腺蛋白质组的种间差异是明显的。鉴定的大部分蛋白质在蛋白质/肽翻译、折叠和保护事件中起作用。然而，最有趣的是，我们证明了蛋白质二硫键异构酶（PDI），催化天然二硫键的形成和异构化的酶的多种异构体的存在。研究不同的PDI亚型是否与不同的毒素家族相互作用，将大大提高我们对锥螺毒素和富含二硫键的肽的产生的认识。
Conotoxins, venom peptides from marine cone snails, diversify rapidly as speciation occurs. It has been suggested that each species can synthesize between 1000 and 1900 different toxins with little to no interspecies overlap. Conotoxins exhibit an unprecedented degree of post-translational modifications, the most common one being the formation of disulfide bonds. Despite the great diversity of structurally complex peptides, little is known about the glandular proteins responsible for their biosynthesis and maturation. Here, proteomic interrogations on the Conus venom gland led to the identification of novel glandular proteins of potential importance for toxin synthesis and secretion. A total of 161 and 157 proteins and protein isoforms were identified in the venom glands of Conus novaehollandiae and Corms victoriae, respectively. Interspecies differences in the venom gland proteomes were apparent. A large proportion of the proteins identified function in protein/peptide translation, folding, and protection events. Most intriguingly, however, we demonstrate the presence of a multitude of isoforms of protein disulfide isomerase (PDI), the enzyme catalyzing the formation and isomerization of the native disulfide bond. Investigating whether different PDI isoforms interact with distinct toxin families will greatly advance our knowledge on the generation of cone snail toxins and disulfide-rich peptides in general.