The structure of the neurotoxin palytoxin determined by MicroED

Abstract

Palytoxin (PTX) is a potent neurotoxin found in marine animals that can cause serious symptoms 17 such as muscle contractions, haemolysis of red blood cells and potassium leakage. Despite years 18 of research, very little is known about the mechanism of PTX. However, recent advances in the 19 field of cryoEM, specifically the use of microcrystal electron diffraction (MicroED), have allowed 20 us to determine the structure of PTX. It was discovered that PTX folds into a hairpin motif and is 21 able to bind to the extracellular gate of Na,K-ATPase, which is responsible for maintaining the 22 electrochemical gradient across the plasma membrane. These findings, along with molecular 23 docking simulations, have provided important insights into the mechanism of PTX and can 24 potentially aid in the development of molecular agents for treating cases of PTX exposure.