Өрмекші уының нейротоксиндері

Group of neurotoxins in spider venom

A latrotoxin is a high molecular mass neurotoxin found in the venom of spiders of the genus Latrodectus (widow spiders) as well as at least one species of another genus in the same family, Steatoda nobilis. 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 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.

The natural occurring α LTX dimer has to form a tetramer to be toxic. Tetramerisation occurs only in the presence of bivalent cations (such as Ca2+ or Mg2+) or amphipathic molecules. The four monomers that form this tetramer are symmetrically arranged around a central axis, resembling a four blade propeller with a diameter of 250 Å and a thickness of 100 Å. The head domains form the compact, central mass brought together and surrounded by the body domains. The wings stand perpendicular towards the axis of the tetramer. Because of this form the tetramer contains a pear shaped channel in the central mass. At the lower end the diameter of this channel is 25 Å, then widens to 36 Å to be constricted to 10 Å at the top.

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 identify two families of important neuronal cell surface receptors. High molecular weight proteins that have been isolated from the Mediterranean black widow (L. tredecimguttatus) include the insect specific neurotoxins α latroinsectotoxin and δ latroinsectotoxin, a neurotoxin affecting crustaceans known as latrocrustatoxin, and small peptides that inhibit angiotensin 1 converting enzyme. whose function has not been explored fully yet, but may be involved in facilitating membrane insertion of latrotoxins.