Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Madrid, Spain; Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA, USA.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Madrid, Spain; Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
Arch Biochem Biophys. 2020 Aug 15;689:108435. doi: 10.1016/j.abb.2020.108435. Epub 2020 May 30.
Actinoporins are a family of pore-forming toxins produced by sea anemones as part of their venomous cocktail. These proteins remain soluble and stably folded in aqueous solution, but when interacting with sphingomyelin-containing lipid membranes, they become integral oligomeric membrane structures that form a pore permeable to cations, which leads to cell death by osmotic shock. Actinoporins appear as multigenic families within the genome of sea anemones: several genes encoding very similar actinoporins are detected within the same species. The Caribbean Sea anemone Stichodactyla helianthus produces three actinoporins (sticholysins I, II and III; StnI, StnII and StnIII) that differ in their toxic potency. For example, StnII is about four-fold more effective than StnI against sheep erythrocytes in causing hemolysis, and both show synergy. However, StnIII, recently discovered in the S. helianthus transcriptome, has not been characterized so far. Here we describe StnIII's spectroscopic and functional properties and show its potential to interact with the other Stns. StnIII seems to maintain the well-preserved fold of all actinoporins, characterized by a high content of β-sheet, but it is significantly less thermostable. Its functional characterization shows that the critical concentration needed to form active pores is higher than for either StnI or StnII, suggesting differences in behavior when oligomerizing on membrane surfaces. Our results show that StnIII is an interesting and unexpected piece in the puzzle of how this Caribbean Sea anemone species modulates its venomous activity.
肌动蛋白孔形成毒素是一类由海葵产生的孔形成毒素，是其毒液鸡尾酒的一部分。这些蛋白质在水溶液中保持可溶性和稳定折叠，但与含有神经鞘磷脂的脂质膜相互作用时，它们成为完整的寡聚膜结构，形成可渗透阳离子的孔，导致细胞通过渗透冲击死亡。肌动蛋白孔形成毒素在海葵基因组中表现为多基因家族：在同一物种中检测到几个编码非常相似的肌动蛋白孔形成毒素的基因。加勒比海葵 Stichodactyla helianthus 产生三种肌动蛋白孔形成毒素（sticholysins I、II 和 III；StnI、StnII 和 StnIII），它们在毒性效力上有所不同。例如，StnII 对绵羊红细胞的溶血作用比 StnI 约强四倍，两者均表现出协同作用。然而，最近在 S. helianthus 转录组中发现的 StnIII 尚未得到表征。在这里，我们描述了 StnIII 的光谱和功能特性，并显示了它与其他 Stns 相互作用的潜力。StnIII 似乎保持了所有肌动蛋白孔形成毒素的良好折叠，其特征是β-折叠含量高，但它的热稳定性显著降低。其功能表征表明，形成活性孔所需的临界浓度高于 StnI 或 StnII，表明在膜表面寡聚化时行为存在差异。我们的研究结果表明，StnIII 是该加勒比海葵物种如何调节其毒性活性之谜中的一个有趣且出乎意料的部分。
