Delta atracotoxin (δ-ACTX-Ar1, robustoxin, or robustotoxin) is a low-molecular-weight neurotoxic polypeptide found in the venom of the Sydney funnel-web spider (Atrax robustus).
Delta atracotoxin produces potentially fatal neurotoxic symptoms in primates, by slowing the inactivation of sodium ion channels in autonomic and motor neurons.
[1] The structure of atracotoxin comprises a core beta region with a cystine knot motif, a feature seen in other neurotoxic polypeptides.
[1][2] Since 1927, records are kept of envenomations of humans by the Sydney funnel-web spider, and 14 deaths have been reported in medical literature between 1927 and 1981, when the antivenom became available.
The structure consists of a small triple-stranded beta-sheet stabilized by a disulfide knot, followed by a C-terminal extension comprising three classic or inverse y-turns.
The 22-28 loop contains one apolar residue, Ala23, and three aromatics, Tyr22, Trp24 and Tyr25, and is flanked by Ile21 at its N-terminus and Trp7 near its C-terminus, so this region represents a significant non-polar surface on the molecule.
d-Atracotoxins induce spontaneous, repetitive firing and prolongation of action potentials resulting in continuous acetylcholine neurotransmitter release from somatic and autonomic nerve endings.
This action is due to voltage-dependent binding to neurotoxin receptor site-3 in a similar, but not identical, fashion to scorpion a-toxins and sea anemone toxins.
These actions underlie the clinical symptoms seen following envenomation and further contribute to the understanding of the molecular basis for activity of this potent neurotoxin on voltage-gated sodium channels.
Studies will contribute to a more detailed mapping of site-3, the neurotoxin receptor site on the sodium-channel and provide structure-activity data critical for determining the phyla-specific actions of this and related atracotoxins.
[8] The bite of a Sydney funnel web spider is at first painful, due to the large fangs and acidic pH of the venom.
Other symptoms include dyspnea and ultimately respiratory failure, generalized skeletal muscle fasciculation, salivation, lachrymation, sweating, nausea, vomiting, diarrhoea, pulmonary edema and pain.
[9] The antivenom was developed by a team headed by Struan Sutherland at the Commonwealth Serum Laboratories (CLS) in Melbourne.
In September 2012, it was reported that stocks of antivenom were running low, and members of the public were asked to catch the spiders so that they could be milked for their venom.
Each vial of the product contains 125 units of antivenom which has been standardized to neutralize 1.25 mg of funnel web spider venom.
There is evidence to show that the antivenom is effective in the treatment of patients bitten by some other funnel web spiders of the genus Hadronyche (formerly Atrax).