Halcurin is a polypeptide neurotoxin from the sea anemone Halcurias sp.[1] Based on sequence homology to type 1 and type 2 sea anemone toxins it is thought to delay channel inactivation by binding to the extracellular site 3 on the voltage gated sodium channels in a membrane potential-dependent manner.[1]
Source and etymology
The polypeptide toxin halcurin is named after its source: the sea anemone genus Halcurias,[1] which are ocean dwelling solitary invertebrates.[2]
Chemistry
The amino acid sequence of halcurin is: VACRCESDGP DVRSATFTGT VDLWNCNTGW HKCIATYTAV ASCCKKD; it consists of 47 amino acids and has a molecular weight of 5,086 Da [1]
General information
A classification of sea anemone polypeptide neurotoxins has been proposed based on their amino acid sequence, dividing the group into three classes of sodium channel toxins.[3] Halcurin is structurally homologous with type 2 toxins, but also has sequence homology to type 1 toxins.[1] Type 1 and 2 toxins are composed of 46 to 49 amino acid residues, and cross-linked by three disulfide bridges.[2] Ten residues including six Cysteine (Cys) residues are completely conserved between type 1 and 2 toxins.[3] Therefore, it is possible that type 1 and 2 toxins have evolved from Halcurin as a common ancestor.[1]
Target
Type 1 and 2 toxins are known to target neurotoxin receptor site 3.[4] Based on the structural homology of halcurin with sea anemone toxin type 1 and 2 [1] it is likely to target neurotoxin receptor site 3.Neurotoxin receptor site 3 is predicted to be at the domain IV of voltage gated sodium channel, more specifically at the extracellular loop of segment 3-4. These voltage gated sodium channels are found in neurons, skeletal muscles, and cardiac muscles.[2]
Mode of action
The domain III and IV intracellular loop structure acts as a fast inactivation gate in voltage gated sodium channels.[5] Sea anemone toxin type 1 and 2 slow or prevent the conformational changes in domain IV segment 3-4 loop required for inactivation of the channel.[6] Based on the structural homology of halcurin to sea anemone neurotoxin type 1 and 2,[1] it is likely to have a similar mode of action.
Toxicity
Halcurin has a median lethal dose (LD50) of 5.8 μg/kg for crabs, but it does not show lethality in mice.[1]