School of Chemical Engineering and Chemistry, Mapua Institute of Technology, Muralla Street Intramuros, Manila 1002, Philippines.
J Proteome Res. 2010 May 7;9(5):2292-301. doi: 10.1021/pr901032r.
Conus species of marine snails deliver a potent collection of toxins from the venom duct via a long proboscis attached to a harpoon tooth. Conotoxins are known to possess powerful neurological effects and some have been developed for therapeutic uses. Using mass-spectrometry based proteomics, qualitative and quantitative differences in conotoxin components were found in the proximal, central and distal sections of the Conus textile venom duct suggesting specialization of duct sections for biosynthesis of particular conotoxins. Reversed phase HPLC followed by Orbitrap mass spectrometry and data analysis using SEQUEST and ProLuCID identified 31 conotoxin sequences and 25 post-translational modification (PTM) variants with King-Kong 2 peptide being the most abundant. Several previously unreported variants of known conopeptides were found and this is the first time that HyVal is reported for a disulfide rich Conus peptide. Differential expression along the venom duct, production of PTM variants, alternative proteolytic cleavage sites, and venom processing enroute to the proboscis all appear to contribute to enriching the combinatorial pool of conopeptides and producing the appropriate formulation for a particular hunting situation. The complementary tools of mass spectrometry-based proteomics and molecular biology can greatly accelerate the discovery of Conus peptides and provide insights on envenomation and other biological strategies of cone snails.
海洋蜗牛的 Conus 物种通过附着在鱼叉牙上的长喙从毒管中输送出一系列强效毒素。已知 Conotoxin 具有强大的神经作用，其中一些已被开发用于治疗用途。使用基于质谱的蛋白质组学，在 Conus textile 毒液管的近端、中央和远端部分发现了 Conotoxin 成分的定性和定量差异，这表明毒液管的各个部分专门用于合成特定的 Conotoxin。反相 HPLC 后，使用 Orbitrap 质谱和 SEQUEST 和 ProLuCID 数据分析鉴定了 31 种 Conotoxin 序列和 25 种翻译后修饰（PTM）变体，其中 King-Kong 2 肽最为丰富。发现了几种以前未报道的已知 Conopeptide 变体，这是首次报道富含二硫键的 Conus 肽中的 HyVal。沿着毒液管的差异表达、PTM 变体的产生、替代蛋白水解切割位点以及在到达喙的过程中的毒液处理似乎都有助于丰富 Conopeptide 的组合库，并为特定的捕猎情况产生适当的配方。基于质谱的蛋白质组学和分子生物学的互补工具可以极大地加速 Conus 肽的发现，并为毒液和其他锥蜗牛的生物策略提供深入了解。
