Black widow spider toxins: the present and the future.
The venom of the black widow spider Latrodectus mactans tredisimguttatus was found to contain a family of high molecular weight toxic proteins inducing a sharp increase in transmitter secretion from the affected nerve endings, which are highly specific for vertebrates, or for insects, or for crustaceans. Along with the known alpha-latrotoxin, five latroinsectotoxins affecting the neurotransmitter release from presynaptic endings of insects and one latrocrustatoxin active only for crustaceans were isolated and studied in detail. Alpha-latrotoxin provokes a massive transmitter release from different nerve endings of vertebrates, whereas other toxins increase the secretion process either in insects or crustaceans. The cDNAs encoding the putative alpha-latrotoxin and two latroinsectotoxins (alpha-latroinsectotoxin and delta-latroinsectotoxin) precursors were cloned and sequenced. These toxins are polypeptides of about 1000 amino acids and share a high level of amino acid identity. Analysis of amino acid sequences of the three toxins reveals the central regions being almost entirely composed of series of ankyrin-like repeats. Taking into account the size and multifunctional properties of latrotoxin its molecule can be divided into several functional domains. Immunochemical experiments indicated the presence in the alpha-latrotoxin molecule of distinguishable functional domains responsible for ionophoric and secretogenic actions. The highly purified preparation of alpha-latrotoxin was shown to contain an additional component, a low molecular weight protein structurally related to crustacean hyperglycemic hormones. Several attempts were made to characterize and isolate alpha-latrotoxin receptor components. The existence of Ca-dependent and Ca-independent binding proteins was found in the presynaptic membrane preparations.
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Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow.
D000595:Amino Acid Sequence; D000818:Animals; D001740:Black Widow Spider; D001921:Brain / Q000187:drug effects; D005544:Forecasting; D008566:Membranes / Q000187:drug effects; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018000:Receptors, Peptide / Q000187:drug effects*; D017386:Sequence Homology, Amino Acid; D013111:Spider Venoms / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000633:toxicity*
D018000:Receptors, Peptide; D013111:Spider Venoms; C034800:alpha-latrotoxin receptor; C020763:alpha-latrotoxin