Halcurin
Halcurin is a polypeptide neurotoxin from the sea anemone Halcurias sp.{{cite journal | last1 = Ishida | first1 =M | title = Halcurin, a polypeptide toxin in the sea anemone Halcurias sp., with a structural resemblance to type 1 and 2 toxins | journal = Toxicon | volume = 35 | pages = 537–544 |pmid= 9133708 | issue=4 |date=Apr 1997 | doi=10.1016/s0041-0101(96)00143-2}} 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.
Source and etymology
The polypeptide toxin halcurin is named after its source: the sea anemone genus Halcurias, which are ocean dwelling solitary invertebrates.{{cite journal | last1 = Bosmans | first1 =F | title = The sea anemone Bunodosoma granulifera contains surprisingly efficacious and potent insect-selective toxins | journal = FEBS | volume = 532 | pages = 131–134 |pmid= 12459477 | issue=1–2 |date=Dec 2002 | doi=10.1016/s0014-5793(02)03653-0| doi-access = free | bibcode =2002FEBSL.532..131B }}
Chemistry
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.{{cite journal | last1 = Norton | first1 =RS | title = Structure and structure-function relationships of sea anemone proteins that interact with the sodium channel | journal = Toxicon | volume = 29 | pages = 1051–1084 |pmid= 1686683 | doi=10.1016/0041-0101(91)90205-6 | year=1991| issue =9 | bibcode =1991Txcn...29.1051N }} Halcurin is structurally homologous with type 2 toxins, but also has sequence homology to type 1 toxins. Type 1 and 2 toxins are composed of 46 to 49 amino acid residues, and cross-linked by three disulfide bridges. Ten residues including six Cysteine (Cys) residues are completely conserved between type 1 and 2 toxins. Therefore, it is possible that type 1 and 2 toxins have evolved from Halcurin as a common ancestor.
Target
Type 1 and 2 toxins are known to target neurotoxin receptor site 3.{{cite journal |last1=Honma |first1=Tomohiro |last2=Shiomi |first2=Kazuo |title=Peptide Toxins in Sea Anemones: Structural and Functional Aspects |journal=Marine Biotechnology |volume=8 |issue=1 |pages=1–10 |year=2006 |pmid=16372161 |doi=10.1007/s10126-005-5093-2 |pmc=4271777|bibcode=2006MarBt...8....1H }} Based on the structural homology of halcurin with sea anemone toxin type 1 and 2 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.
Mode of action
The domain III and IV intracellular loop structure acts as a fast inactivation gate in voltage gated sodium channels.{{cite journal | last1 = Caterall | first1 =WA | title = Structure and function of voltage-gated ion channels | journal = Annual Review of Biochemistry | volume = 64 | pages = 493–531 |pmid= 7574491 | doi=10.1146/annurev.bi.64.070195.002425 | year=1995}} 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.{{cite journal | last1 = Rogers | first1 =JC | title = 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 = Journal of Biological Chemistry | volume = 271 | pages = 15950–15962 |pmid= 8663157 | issue=27 |date=Jul 1996 | doi=10.1074/jbc.271.27.15950| doi-access = free }} Based on the structural homology of halcurin to sea anemone neurotoxin type 1 and 2, 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.
References
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External links
- [https://www.uniprot.org/uniprot/P0C5G6 Uniprot Halcurin (P0C5G6) ]
{{Toxins}}
{{Sodium channel blockers}}