Zhang Han, Pan Xinghua, Weigang Chen
Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, No. 1023-1063, Satai South Road, Baiyun District, Dongguan, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Sci Rep. 2025 Apr 8;15(1):12061. doi: 10.1038/s41598-025-96976-7.
Exploring sea anemone polypeptides enables us to understand the evolutionary history and ecological adaptation strategies of species at the microscopic level. More importantly, it aims to provide a solid theoretical foundation for drug development and biodiversity conservation research. Through systematic research, we discovered a total of 51 toxin sequences in species Anthopleura midori and Acyinia equina. The toxin sequences between the two species exhibited significant differences, with notable diversity observed among individuals. In terms of genetic diversity, species Anthopleura midori primarily exhibits variations due to single nucleotide polymorphisms (SNPs), whereas species Actinia equina shows frequent insertion and deletion events. In transcription factor analysis, both species Anthopleura midori and Actinia equina share common transcription factors TEA (TEA Domain Transcription Factor), SPL(Squamosa Promoter Binding Protein-like), and bHLH (Basic Helix-Loop-Helix). Notably. Notably, bHLH is highly expressed in Actinia equina, which may give it advantages in muscle and nervous system development. On the other hand, Anthopleura midori may rely on other transcription factors. Furthermore, by employing transcriptomics and mass spectrometry techniques, two new gene families were successfully identified, and five structurally novel cyclic peptides were predicted. Kinetic simulations further confirmed that the peptide segment B3a-c29555_c4_g4 binds primarily through hydrogen bonds and hydrophobic interactions with the Cav3.1 (PDB ID:6 KZO) protein, and this peptide has the potential to act as a channel modulator for Cav3.1. Overall, this research not only deepens our understanding of the genetic basis of toxin diversity but also highlights the great potential of these toxins in the development of novel drugs.
探索海葵多肽使我们能够在微观层面了解物种的进化历史和生态适应策略。更重要的是，其目的是为药物开发和生物多样性保护研究提供坚实的理论基础。通过系统研究，我们在绿疣海葵和马氏海葵物种中总共发现了51个毒素序列。这两个物种之间的毒素序列存在显著差异，个体间观察到明显的多样性。在遗传多样性方面，绿疣海葵物种主要表现为单核苷酸多态性（SNP）引起的变异，而马氏海葵物种则显示出频繁的插入和缺失事件。在转录因子分析中，绿疣海葵和马氏海葵物种都共享常见的转录因子TEA（TEA结构域转录因子）、SPL（类Squamosa启动子结合蛋白）和bHLH（碱性螺旋-环-螺旋）。值得注意的是，bHLH在马氏海葵中高度表达，这可能使其在肌肉和神经系统发育中具有优势。另一方面，绿疣海葵可能依赖其他转录因子。此外，通过采用转录组学和质谱技术，成功鉴定了两个新的基因家族，并预测了五个结构新颖的环肽。动力学模拟进一步证实，肽段B3a-c29555_c4_g4主要通过氢键和疏水相互作用与Cav3.1（PDB ID：6KZO）蛋白结合，并且该肽有潜力作为Cav3.1的通道调节剂。总体而言，这项研究不仅加深了我们对毒素多样性遗传基础的理解，还突出了这些毒素在新型药物开发中的巨大潜力。
