alpha bungarotoxin Flashcards
where does alpha bungarotoxin bind
Postsynaptic AChRs at neuromuscular junction
structure of the receptor
ligand-gated ion channel found at the neuromuscular junction of vertebrates and electrocytes of electric fish.
4 transmembrane glycoprotein subunit = forming a alpha2betagamma(e) pentameric complex
binding happens at the alpha site of the glycoprotein between residue 172-205
MOA
Antagonistic binding to nAChRs; blocks the cholinergic receptors at the neuromuscular junction; bind to the outer vestibule and contacts the surface of the surface membrane bilayer + neuronal alpha 7 nAChRs.
irreversible binding to the nAChRs
aBtx-
Effects of the toxin
- Binding to neuromuscular junction cholinergic receptors causes paralysis, failure and eventually death in the victim because the post synapse does not recieve the firing of AChs
- Blocking alpha 7 nAChRs involved in the cholinergic anti-inflammatory pathway The activation of α7nAChR can lead to calcium influx directly, which can trigger neurotransmitter release, action potentials, synaptic plasticity, and calcium-induced calcium release. It can also activate the JAK2-STAT3 signaling pathway and further induce anti-apoptotic and anti-inflammatory effects.
- α Bungarotoxin binds irreversibly to the nAChR and the complex bungarotoxin—nAChR is immunogenic, which may result in production of autoimmune antibodies. For this reason, α bungarotoxin is a suitable experimental model for myasthenia gravis
structure of the toxin
three finger toxin (long chain neurotoxin) - 5 disulfide bond and 74 amino acid residue; 2nd finger is important for specificity and affinity
Toxin to therapeutics -aBtx
Help clinical research of the structure and binding of the nAChRs; helps with the identification of the structure and function of cholingeric receptors;
Labelling alpha bungarotoxin with fluorescent or radioactive tag to observe the distribution n localisation of the nAChRs; Research to identify if alpha –BGT binds to nervous tissues
