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PROSITE documentation PDOC60018 |
Delta-atracotoxins (ACTXs) are peptide toxins isolated from the venom of Australian funnel-web spiders that inhibit conversion of the sodium channel from the open to the inactivated state, resulting in sodium current remaining at membrane potentials where inactivation is normally complete. They induce spontaneous repetitive firing and prolongation of action potentials resulting in neurotransmitter release from somatic and autonomic nerve endings. This results from a selective slowing of tetrodotoxin (TTX) voltage-gated sodium channel inactivation and a hyperpolarizing shift of the voltage-dependence of activation. This action is due to voltage-dependent binding to neurotoxin receptor site-3 [1,2].
All delta-ACTXs are highly homologous 42-residue peptides with no significant sequence homology with any presently known neurotoxins. The toxins have a high proportion of basic residues and are cross-linked by four conserved intramolecular disulfide bonds. Delta-ACTXs comprise a core β region containing a triple-stranded antiparallel β-sheet and a thumb-like extension protruding from the β region (see <PDB:VTX>) [1,2]. The β region of delta-ACTXs contains a 'disulfide-knot', which places them in a class of toxins and inhibitory polypeptides with 'an inhibitor cystine-knot' (ICK) motif [3].
The delta-ACTX family includes:
Delta-ACTX family proteins have a [C-C-CCC-C-C-C] cysteine arrangement. The three dimensional structure of delta-ACTXs possesses a knottin scaffold (see <PDOC60004>) [E1] with a fourth pair (I-IV) of cysteine residues (marked '#' in the following schematic representation) involved in an additional disulfide linkage. The cystine-knot motif in delta-ACTXs provides high stability and maintains the tertiary structure.
+----------------+ | +--------------|-----------+ # |#| | | CxxxxxxCxxxxxCCCxxxCxxxxxxxxxxCxxxxxxxxxxxC | | | | +------|------+ | +-----------+
'C': conserved cysteine involved in disulfide bond '#': fourth pair of the cysteine residue
Our signature pattern for delta-ACTXs contains the eight conserved cysteines involved in disulfide bonds.
Last update:June 2005 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
1 | Authors | Szeto T.H. Birinyi-Strachan L.C. Smith R. Connor M. Christie M.J. King G.F. Nicholson G.M. |
Title | Isolation and pharmacological characterisation of delta-atracotoxin-Hv1b, a vertebrate-selective sodium channel toxin. | |
Source | FEBS Lett. 470:293-299(2000). | |
PubMed ID | 10745084 |
2 | Authors | Nicholson G.M. Little M.J. Birinyi-Strachan L.C. |
Title | Structure and function of delta-atracotoxins: lethal neurotoxins targeting the voltage-gated sodium channel. | |
Source | Toxicon 43:587-599(2004). | |
PubMed ID | 15066415 | |
DOI | 10.1016/j.toxicon.2004.02.006 |
3 | Authors | Pallaghy P.K. Nielsen K.J. Craik D.J. Norton R.S. |
Title | A common structural motif incorporating a cystine knot and a triple-stranded beta-sheet in toxic and inhibitory polypeptides. | |
Source | Protein Sci. 3:1833-1839(1994). | |
PubMed ID | 7849598 |
E1 | Source | http://knottin.cbs.cnrs.fr |