Close Menu
Science & Technology

Black Widow spider venom forms a needle shape to penetrate the cell

The Black Widow spider is well renowned for its distinctive hourglass shape and venomous bite. The Venom of the black widow is a neurotoxin with latrotoxins as its main component.

While the bite from a black widow is deadly for insects, it’s rarely fatal in healthy human adults. This venom is an amalgamation of seven latrotoxins (LTXs), among which, only α-latrotoxin, targets vertebrates.

α-latrotoxin is known to interfere with signal transmission in the nervous system. When it binds with nerve receptors, α-latrotoxin causes an uncontrolled flow of calcium ions, releasing neurotransmitters. This causes strong muscle contractions and spasms.

While the process appears pretty simple, there is a complex chain of mechanisms. Scientists at the University of Münster think studying the mechanism of LTX is of significant medical relevance, potentially leading to the development of biotechnological applications and biopesticides.

Therefore, scientists have deciphered the structure of α-latrotoxin and observed it at atomic resolution using high-performance cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) computer simulations.

Identifying the genes behind venom production

The images show that a part of the toxin undergoes a mushroom-shaped transformation and penetrates the domain of the cell membrane like a needle. This penetration forms a tiny opening in the cell membrane which enables the calcium ions to flow into the cell.

The precursor of α-LTX is activated by proteolytic cleavage of its inhibitory terminal domains in the venom gland. Tetramerization, a prerequisite for pore formation, may be enhanced through association with presynaptic receptors. A central Ca2+ binding site brings the HBD domains into close proximity. The C-terminal helices of the HBDs, along with the CD domains, reorient to form a tetrameric coiled-coil stalk. The N-terminal helices of this stalk, stabilized by disulfide bridges, insert into the membrane, forming a cation-permeable transmembrane channel.The precursor of α-LTX is activated by proteolytic cleavage of its inhibitory terminal domains in the venom gland. Tetramerization, a prerequisite for pore formation, may be enhanced through association with presynaptic receptors. A central Ca2+ binding site brings the HBD domains into close proximity. The C-terminal helices of the HBDs, along with the CD domains, reorient to form a tetrameric coiled-coil stalk. The N-terminal helices of this stalk, stabilized by disulfide bridges, insert into the membrane, forming a cation-permeable transmembrane channel.
The precursor of α-LTX is activated by proteolytic cleavage of its inhibitory terminal domains in the venom gland. Tetramerization, a prerequisite for pore formation, may be enhanced through association with presynaptic receptors. A central Ca2+ binding site brings the HBD domains into close proximity. The C-terminal helices of the HBDs, along with the CD domains, reorient to form a tetrameric coiled-coil stalk. The N-terminal helices of this stalk, stabilized by disulfide bridges, insert into the membrane, forming a cation-permeable transmembrane channel.

The study explains the working of α-latrotoxin, which clearly behaves way differently than known toxins.

“The toxin mimics the function of the calcium channels of the presynaptic membrane in a highly complex way. It therefore differs in every respect from all previously known toxins,” explains Christos Gatsogiannis.

Ants use neurotoxins to inflict pain on their victims

The new findings provide mechanistic insights into the process of α-LTX integration, opening up a wide range of potential applications. Researchers have expressed that latrotoxins have considerable biotechnological potential, including the development of antidotes, treatments for paralysis, and new biopesticides.

Journal Reference

  1. Klink, B. U., Alavizargar, A., Kalyankumar, K. S., Chen, M., Heuer, A., & Gatsogiannis, C. (2024). Structural basis of α-latrotoxin transition to a cation-selective pore. Nature Communications, 15(1), 1-13. DOI: 10.1038/s41467-024-52635-5



Source

Share.

Related News