PROSITE documentation PDOC60016

Omega-atracotoxin (ACTX) families signatures

Omega-atracotoxins (ACTX) form a family of neurotoxins that block insect but not vertebrate voltage-gated calcium channels. Omega-ACTXs are environmentally benign, insect-specific toxins that represent excellent leads for the development of new pesticides. Omega-ACTXs comprise a disulfide-rich region that has a [C-C-CC-C-C] arrangement and possess a Knottin scaffold (see <PDOC60004>) [1,2,3,4,5].

The omega-ACTX type 1 family contains 36 to 37-residue toxins with three highly conserved but structurally disordered N-terminal residues, which precede the first cysteine residue (see <PDB:1AXH>) [1,2,3,5]. This family includes:

• Omega-ACTX Hv1a, Hv1b, Hv1c, Hv1d, Hv1e, Hv1f from Hadronyche versuta (Blue mountains funnel-web spider) (Atrax versutus),
• Omega-ACTX Ar1a from Atrax robustus (Funnel-web spider),
• Omega-missulenatoxin-Mb1a from Missulena bradleyi (Eastern mouse spider).

The omega-ACTX type 2 family contains 43 to 45-residue toxins with a disordered C-terminal lipophilic extension (see <PDB:1G9P>) [4,5]. This family includes:

 - Omega-ACTX  Hv2a from Hadronyche versuta (Blue mountains funnel-web spider)
   (Atrax versutus),
 - Omega ACTX As2a, As2b from Atrax sp. Illawarra (Funnel-web spider),
 - Omega  ACTX  Hi2a,  Hi2b  from Hadronyche infensa (Fraser island funnel-web
   spider).

                                   +------------------+
                                   |                  |
                      ********     ######             |
                   xxxCxxxxxxCxxxxxCCxxxCxxxxxxxxxxxxxC
                      |      |      |   |
                      +------|------+   |
                             +----------+

'C': conserved cysteine involved in a disulfide bond.
'*': position of the pattern for type 1.
'#': position of the pattern for type 2.

We developed two signature patterns for omega-ACTXs, one for the type 1 family and one for the type 2 family.