[4] The venom of widow spiders (Latrodectus) contains several protein toxins, called latrotoxins, which selectively target either vertebrates, insects or crustaceans.
α-LTX has a high affinity for receptors that are specific for neuronal and endocrine cells of vertebrates.
This precursor molecule undergoes post-translational processing where the eventual, active α-LTX protein (131.5 kDa) is formed.
[6] The N-terminus of the α-LTX precursor molecule is preceded by short hydrophilic sequences ending with a cluster of basic amino acids.
These clusters are recognized by proteolytic enzymes (furin-like proteases), which cleave and activate the α-LTX precursor molecules by means of hydrolysis.
The cytosolic α-LTX precursor molecule is released from the cell by means of holocrine secretion where it ends up in the venom gland of the spider.
The onset of effects by intoxication can occur with a lag-period of 1 to 10 minutes, even at subnanomolar concentration levels.
[7][9] Stimulation of small end-plate action potentials are initially induced by the neurotoxin, while later on the neurotransmission is blocked at the neuromuscular junction.
[8] The four heads of the tetramer form a bowl surrounding the pore, which is restricted at one point to 10 Å.
Biological membranes block pore formation when no α-LTX receptors are present (neurexin, latrophilin, PTPσ).
Further membrane potential disturbances occur due to permeability of small molecules, such as neurotransmitters and ATP to pass through the α-LTX pore.
[citation needed] The natural occurring α-LTX dimer has to form a tetramer to be toxic.
[7][8] The base of the tetramer (below the wings) is 45 Å deep and is hydrophobic, which mediates insertion into the cell membrane.
Also insertion of the tetramer is only possible in presence of certain receptors (mainly neurexin Iα and latrophilin and PTPσ in a minor extent) on the membrane.
[8] The LD50 of Latrodectus venom in mg/kg for various species: frog = 145, blackbird = 5.9, canary = 4.7, cockroach = 2.7, chick = 2.1, mouse = 0.9, housefly = 0.6, pigeon = 0.4, guinea-pig = 0.1.
[12] αLTX has helped confirm the vesicular transport hypothesis of transmitter release, establish the requirement of Ca2+ for vesicular exocytosis, and characterize individual transmitter release sites in the central nervous system.
It helped the approach to deciphering the intracellular signaling transduction mechanism stimulated by αLTX.