Recently, scientists in China revealed the strategy of centipede subdue giant prey by the solving solution structure of its peptide toxin SsTx.

Centipedes are carnivorous and venomous animals, widely distributed in all continents except Antarctica and their prey, defense and other life activities mostly depend on its venom. Centipedes can prey on small mammals, rodents, amphibians and reptiles, whose weight are far greater than their own.

Patients who have been bitten by centipede may experience pain, edema, inflammation, necrosis and subcutaneous hemorrhage and in severe cases, and they may have clinical symptoms such as hypertension, myocardial ischemia, respiratory failure, coma and spasticity, even death.

Recently, a joint research team from High Magnetic Field Laboratory, Chinese Academy of Sciences, or CHMFL, Kunming Institute of Zoology and Huazhong University of Science and Technology discovered that the Chinese red-headed centipede (Scolopendra subspinipes mutilans) can rapidly subdue and prey on preys which are 30 times larger within 30 seconds.

In this study, they found that this amazing predation efficiency is due to a K+ ion channel KCNQ inhibitor in their venom, which is SsTx, a peptide toxin.

SsTx causes dysfunction of brain, lung and heart of preys through blocking KCNQ. Based on the molecular mechanism of this process, scientists tried to treat heart failure caused by centipede poisoning by using a drug called Retigabine.

Good results have been obtained in animal models of disease, providing treatments for such diseases.

Dr. WU Fangming from CHMFL successfully solved the three-dimensional structure of the 53-amino acid toxin SsTx using solution NMR.

The structure provided a solid structural basis for the subsequent study of the interaction between the toxin and its targeted K+ ion channel KCNQ.

On the other hand, the results of this work demonstrate the advantages of solution NMR in resolving the three-dimensional structures of polypeptide toxins.

Just a few milligrams of pure peptide samples are sufficient to obtain the 3D structure of the peptide toxin, without the need for expression, crystallization and isotope labeling. So far, the largest peptide toxin we had solved by this method is 57-amino acid Manbalgin-1.

The study entitled "Centipedes subdue giant prey by blocking KCNQ channels" was published online at PNAS.

This paper drew a wide range of attentions. A series of academic comments and summary reports were published by SCIENCE, Science Magazine, Xinhua News Agency, Newsweek, Washington Post, German Press Agency, Daily Planet (Canada), and Chemistry world (Britain).

Centipedes subdue giant prey through its peptide toxin SsTx interacting with K+ ion channel KNCQ. A) Image of a S. subspinipes mutilans preying on a Kunming mouse. B) Molecular docking of SsTx onto KCNQ4. The side chains of 12R/13K in SsTx and D266/D288 in KCNQ4 are shown. (C) Representative vascular contractility of thoracic aorta when challenged sequentially with 5 M SsTx and 40 M RTG. (Image by the research team)