Α-latrotoxin

A latrotoxin is a high-molecular mass neurotoxin found in the venom of spiders of the genus Latrodectus (widow spiders). Latrotoxins are the main active components of the venom and are responsible for the symptoms of latrodectism.

The following latrotoxins have been described: five insecticidal toxins, termed α, β, γ, δ and ε-latroinsectotoxins, one vertebrate-specific neurotoxin, alpha-latrotoxin, and one toxin affecting crustaceans, α-latrocrustatoxin.

The best-studied latrotoxin is alpha-latrotoxin, which acts presynaptically to release neurotransmitters (including acetylcholine) from sensory and motor neurons, as well as on endocrine cells (to release insulin, for example). It is a ~130 kDa protein that exists mainly in its dimerized or tetramerized forms.

α-Latrotoxin (α-LTX) can naturally be found in widow spiders of the genus Latrodectus. The most widely known of those spiders are the black widows, Latrodectus mactans. The venom of widow spiders (Latrodectus) contains several protein toxins, called latrotoxins, which selectively target against either vertebrates, insects or crustaceans. One of these toxins is α-latrotoxin and targets selectively against vertebrates; it is ineffective in insects and crustaceans. α-LTX has a high affinity for receptors that are specific for neuronal and endocrine cells of vertebrates.

As the DNA sequence for α-LTX is transcribed and translated, an inactive precursor molecule of α-LTX (156.9 kDa) is formed. This precursor molecule undergoes post-translational processing where the eventual, active α-LTX protein (131.5 kDa) is formed.

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 C-terminus too is recognized by these furin-like proteases and is also cleaved.

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