How black widow venom attacks the nervous system

The black widow is one of the most feared spider species, and is widely associated with danger. This eight-legged marvel has earned its terrifying reputation through a venom that’s a potent cocktail of seven distinct toxins.

Each toxin found in black widow venom targets the nervous system in a unique way. Among these substances, α-latrotoxin stands out. It is known to paralyze insects and crustaceans, and is poisonous to humans.

Black widow’s potent potion

The α-latrotoxin operates by latching onto specific receptors dotted across the synapses. These are the contact points between nerve cells or between nerve cells and muscles.

Once attached, it triggers the uncontrollable flow of calcium ions into the presynaptic membranes of the signaling cells. This sets off the release of neurotransmitters and ushers in strong muscle contractions and spasms.

Despite this seemingly straightforward process, what lies beneath is a highly complex mechanism. A team of scientists at the University of Münster has now deciphered the structure of α-latrotoxin before and after membrane insertion at near atomic resolution

An insightful discovery

The scientific endeavor was led by experts at the Center for Soft Nanoscience, including Professor Christos Gatsogiannis in the Institute of Medical Physics and Biophysics and Professor Andreas Heuer in the Institute of Physical Chemistry.

To investigate the the mechanism of calcium influx into the presynaptic membrane, the experts used a combination of high-performance cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) computer simulations.

And their finding? The α-latrotoxin, in a fascinating display of transformation, forms a stalk – penetrating the cell membrane akin to a syringe – upon binding to the receptor.

This stalk carves out a small pore that functions as a calcium channel in the membrane. But there’s more. MD simulations revealed that calcium ions flow into the cell through a selective gate located right above the pore.

This new understanding of the hidden mechanisms of α-latrotoxin provides profound insights.

“The toxin mimics the function of the calcium channels of the presynaptic membrane in a highly complex manner, differing completely from all previously known toxins,” said Professor Gatsogiannis.

Practical applications

Such breakthroughs bring more than just knowledge; they open the door to a host of practical applications.

Latrotoxins possess considerable biotechnological potential that could support the creation of enhanced antidotes, therapies for paralysis, and novel biopesticides.

The research group led by Professor Gatsogiannis previously cracked the code on the structure of insect-specific latrotoxins in the venom of the black widow spider before their insertion into the membrane.

Harnessing black widow venom

While the venom of the black widow may seem like something to be avoided, its unique properties have captured the interest of scientists looking to harness its power for medical and biotechnological advancements.

“Taken together, these data give insight into a unique mechanism for membrane insertion and channel formation, characteristic of the LTX family, and provide the necessary framework for advancing novel therapeutics and biotechnological applications,” wrote the researchers.

Understanding α-latrotoxin’s structure and function opens doors to different applications that could turn this venom from a deadly threat into a potential lifesaver.

One area of potential lies in the development of more efficient antivenoms. Current treatment for black widow bites involves pain relief and supportive care. While antivenoms are available, they are not always effective.

With the knowledge on how α-latrotoxin interacts with human nerve cells, researchers can design targeted antivenoms that neutralize the toxin before it causes damage to the nervous system.

Potential therapeutic use of venom

The venom’s ability to selectively bind to certain receptors also suggests potential therapeutic uses. For instance, researchers are exploring how modified versions of α-latrotoxin could treat conditions involving muscle spasms or paralysis by targeting specific neural pathways.

Additionally, the venom’s pore-forming mechanism could inspire new designs for biopesticides, selectively targeting pests without harming other species.

Research into black widow venom continues to demonstrate that even the most fearsome elements of nature can offer unexpected benefits, transforming something feared into a source of healing and innovation.

The study is published in the journal Nature Communications.

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