HgeTx1 (systematic name: α-KTx 6.14) is a toxin produced by the Mexican
scorpion ''
Hoffmanihadrurus gertschi'' that is a reversible blocker of the ''
Shaker
Shaker or Shakers may refer to:
Religious groups
* Shakers, a historically significant Christian sect
* Indian Shakers, a smaller Christian denomination
Objects and instruments
* Shaker (musical instrument), an indirect struck idiophone
* Cock ...
B'' K
+-channel, a type of
voltage-gated potassium channels.
Etymology and Source
The toxin HgeTx1 is produced by the Mexican scorpion ''
Hoffmanihadrurus gertschi'', which belongs to the family of
Caraboctonidae
The Caraboctonidae (hairy scorpions) are part of the superfamily Iuroidea. The family was established by Karl Kraepelin in 1905.
List of genera and species
* '' Hadrurus''
** '' H. arizonensis''
** '' H. spadix''
References
{{Taxonbar, ...
.
HgeTx1 is the first toxin (Tx1) from this scorpion (Hge).
HgeTx1 belongs to the
α-KTx potassium channel toxin category, and is placed in the sixth subfamily of all α-KTx toxins where HgeTx1 is the fourteenth member, which gives HgeTx1 its systematic name α-KTx 6.14.
Chemical Structure
All α-KTx category toxins are peptides that contain between 20 and 40 amino acids and contain three or four
disulfide bridges. HgeTx1 consists of 36 amino acids and has four disulfide bridges. These disulfide bridges exist between
Cys
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, som ...
1–Cys5, Cys2–Cys6, Cys3–Cys7 and Cys4–Cys8. It has a
molecular mass of 3950 atomic mass units.
Target
Electrophysiological experiments (whole cell configuration
patch clamping) have been performed to investigate the physiological effect of HgeTx1 on ''Shaker B'' K
+-channels in insect cell cultures. These recordings show that HgeTx1 reversibly blocks the ''Shaker B'' K
+-channel. This blockage follows a
Michaelis-Menten saturation relationship with a
Kd of 52 nM.
However, there is no report of selectivity for or blockage of other subtypes of K
+-channels.
Mode of action
HgeTx1 has only been investigated for its effectiveness on the ''Shaker B'' K
+-channel, where the toxin seems to work as a plug that blocks the pore's ion conductance. This blockage follows the functional dyad model
that underlies most α-KTx toxins. In the functional dyad model, a
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
residue interacts with a hydrophobic
Leu,
Tyr,
Met or
Phe residue, in order to recognize the K
+-channel. On the extracellular side of the channel, the side-chain of the lysine residue will enter the pore and subsequently block the channel. In HgeTx1, it seems likely that the Lys24 residue will interact with the hydrophobic Met33 or Leu34 residue according to the functional dyad model, which allows it to block the ''Shaker B'' K
+-channel.
Toxicity
Scorpions of the family Caraboctonidae, each of which produce a cocktail of different toxins, are not considered dangerous to humans.
References
{{Potassium channel blockers
Ion channel toxins
Neurotoxins
Scorpion toxins