Black widow spider toxins: the present and the future.
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow.
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.
PMID: 9792186 [PubMed - indexed for MEDLINE]