Abstract:
Palytoxin (PTX) is a potent neurotoxin found in marine animals that can cause serious symptoms such as muscle contractions, haemolysis of red blood cells and potassium leakage. Despite years of research, very little is known about the mechanism of PTX. However, recent advances in the field of cryoEM, specifically the use of microcrystal electron diffraction (MicroED), have allowed us to determine the structure of PTX. It was discovered that PTX folds into a hairpin motif and is able to bind to the extracellular gate of Na,K-ATPase, which is responsible for maintaining the electrochemical gradient across the plasma membrane. These findings, along with molecular docking simulations, have provided important insights into the mechanism of PTX and can potentially aid in the development of molecular agents for treating cases of PTX exposure.
摘要:
Palytoxin(PTX)是一种在海洋动物中发现的强效神经毒素,可引起肌肉收缩等严重症状,红细胞溶血和钾渗漏。尽管经过多年的研究,对PTX的机制知之甚少。然而,冷冻EM领域的最新进展,特别是使用微晶电子衍射(MicroED),使我们能够确定PTX的结构。发现PTX折叠成发夹基序,能够与Na的细胞外门结合,K-ATP酶,负责维持跨质膜的电化学梯度。这些发现,以及分子对接模拟,提供了对PTX机制的重要见解,并可能有助于开发用于治疗PTX暴露病例的分子药物。