Halcurin is a polypeptide
neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and matur ...
from the
sea anemone ''
Halcurias'' sp.
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
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
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.]
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 [
]
General information
A classification of sea anemone polypeptide neurotoxins
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature nerv ...
has been proposed based on their amino acid sequence, dividing the group into three classes of sodium channel 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
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, s ...
(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
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and matur ...
receptor site 3. Based on the structural homology of halcurin with sea anemone toxin type 1 and 2 [ it is likely to target ]neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and matur ...
receptor site 3.
Neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and matur ...
receptor site 3 is predicted to be at the domain IV of voltage gated sodium channel
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chann ...
, more specifically at the extracellular loop of segment 3-4. These voltage gated sodium channels
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
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
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
. 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.sea anemone neurotoxin
Sea anemone neurotoxin is the name given to neurotoxins produced by sea anemones with related structure and function.
Sea anemone neurotoxins can be divided in two functional groups that either specifically target the sodium channel or the potas ...
type 1 and 2,[ it is likely to have a similar mode of action.
]
Toxicity
Halcurin has a median lethal dose
In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is ...
(LD50) of 5.8 µg /kg for crabs, but it does not show lethality in mice.[
]
References
External links
Uniprot Halcurin (P0C5G6)
{{Sodium channel blockers
Neurotoxins
Ion channel toxins
Sea anemone toxins