Halcurin Explained

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]

External links

• Uniprot Halcurin (P0C5G6)

Notes and References

1. Ishida . M . Halcurin, a polypeptide toxin in the sea anemone Halcurias sp., with a structural resemblance to type 1 and 2 toxins . Toxicon . 35 . 537–544 . 9133708 . 4 . Apr 1997 . 10.1016/s0041-0101(96)00143-2.
2. Bosmans . F . The sea anemone Bunodosoma granulifera contains surprisingly efficacious and potent insect-selective toxins . FEBS . 532 . 131–134 . 12459477 . 1–2 . Dec 2002 . 10.1016/s0014-5793(02)03653-0. free .
3. Norton . RS . Structure and structure-function relationships of sea anemone proteins that interact with the sodium channel . Toxicon . 29 . 1051–1084 . 1686683 . 10.1016/0041-0101(91)90205-6 . 1991. 9 .
4. Honma . Tomohiro . Shiomi . Kazuo . Peptide Toxins in Sea Anemones: Structural and Functional Aspects . Marine Biotechnology . 8 . 1 . 1–10 . 2006 . 16372161 . 10.1007/s10126-005-5093-2 . 4271777.
5. Caterall . WA . Structure and function of voltage-gated ion channels . Annual Review of Biochemistry . 64 . 493–531 . 7574491 . 10.1146/annurev.bi.64.070195.002425 . 1995.
6. Rogers . JC . Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit . Journal of Biological Chemistry . 271 . 15950–15962 . 8663157 . 27 . Jul 1996 . 10.1074/jbc.271.27.15950. free .