Latrodectus spiders, known commonly as black widows, produce a deadly venom containing neurotoxins to incapacitate or kill their prey. The specific subclass of neurotoxins produced by black widow spiders, known as latrotoxins (LaTXs), make their bites especially dangerous and even potentially fatal to humans. Researchers at the University of Münster, the Max Planck Institute and Jacobs University Bremen have now uncovered the molecular structure of latrotoxins for the first time using cryogenic electron microscopy (cryo-EM), which could pave the way for future studies and applications in areas such as medicine and agriculture.
The venom of Latrodectus spiders contains a cocktail of seven LaTXs total: five that target insects, one that targets crustaceans and one that targets vertebrates. For this study, the researchers examined the δ-latroinsectotoxin and α-latrocrustatoxin using cryo-EM, which allowed the three-dimensional structure of the biomolecules to be imaged in near-atomic resolution. Revealing the specific chemical architecture of these neurotoxins allows scientists to better understand how exactly the toxins recognize and attach to specific receptors on the surface of a cell, said corresponding author Christos Gatsogiannis.
The studies revealed that the structure of LaTXs differs from that of other toxins, and this insight could lead to possible new applications in medicine and in the development of insecticides. Although human deaths from black widow bites are rare, they can also lead to severe symptoms such as muscle spasms, abdominal pain and nausea; further study of vertebrate-specific LaTXs can aid in the development of more effective antidotes. This research was published in Nature Communications.
“The general structure of LaTX is unique and is different in every possible way from all other known toxins,” said Gatsogiannis. “At the moment we are studying the structure of all members of the latrotoxin family - in particular how they exactly recognise the specific receptors on the surface of the cell, and how these sensors function.”
The researchers noted that the capabilities of cryo-EM were essential to elucidating the complex architecture of the neurotoxin, and plan to introduce the technology at Münster University’s newest research building in the near future.
“The practical importance for medical research is immense, as ‘function’ is directly linked to ‘structure’ in a biological context,” said Minghao Chen, the study’s lead author. “But the method is highly complex and requires an ultramodern infrastructure.”
Photo: The team used cryo-electron microscopy to reveal the structures of toxins specific to insects and crustaceans (right) from the black widow spider (left). Credit: nickybay.com, Gatsogiannis team