Lq2 is a component of the venom of the

scorpion Scorpions are predatory arachnids of the order Scorpiones. They have eight legs, and are easily recognized by a pair of grasping pincers and a narrow, segmented tail, often carried in a characteristic forward curve over the back and always end ...

Leiurus quinquestriatus The deathstalker (''Leiurus quinquestriatus'') is a species of scorpion, a member of the family Buthidae. It is also known as the Palestine yellow scorpion, Omdurman scorpion, Naqab desert scorpion and by many other colloquial names, which gen ...

''. It blocks various potassium channels, among others the

inward-rectifier potassium ion channel Inward-rectifier potassium channels (Kir, IRK) are a specific lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are activated by phosphatidylinos ...

ROMK The renal outer medullary potassium channel (ROMK) is an ATP-dependent potassium channel (Kir1.1) that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb (TAL) and potassium secretion ...

Alternative names

Lq2 is also known as Potassium channel toxin alpha-KTx 1.2, Charybdotoxin-2, ChTX-Lq2, ChTx-d, Toxin 18-2 or Lqh 18-2.

Etymology

The name Lq2 refers to the name of the animal species in which the toxin can be found. Lq2 can be found in the

'' (Lq). Lq2 is structurally similar to Lq1, which had been found previously and which is also a potassium channel blocker.

Sources

Lq2 is a component of the venom of the scorpion Leiurus quinquestriatus, known under various names, for example the deathstalker, the Israeli desert scorpion or the yellow scorpion.

Structure

Lq2 is a small peptide of 37 amino acids. Lq2 contains the classical scorpion toxin alpha-beta scaffold and is structurally similar to the neurotoxin

Charybdotoxin Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion '' Leiurus quinquestriatus hebraeus'' (''deathstalker'') that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous syst ...

(CTX). Lq2 consists of an

α-helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...

and a

β-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

, connected by an αβ3 loop containing disulfide bridges. The proteins three-dimensional structure has been reconstructed using nuclear magnetic resonance techniques.

Target

Lq2 interacts with all three types of potassium channels: the voltage-activated, the Ca²⁺- activated and the inward-rectifier potassium channels. The unique trait of Lq2 is its high affinity for certain inward-rectifier potassium ion channels, especially the Renal Outer Medullary Potassium channel ROMK1. This ion channel contributes to the regulation of the resting membrane potential.

Mode of action

Since all potassium channels share the same ion conducting outer pore structure, Lq2 binds to all three potassium channel types. Lq2 interacts with the T-X-X-T-X-GT-X-X-T-X-GY/F-Gt K+-selective section within the pore-forming region (P-region) of the ROMK1 ion channel. It blocks the channel, binding in a 1:1 stoichiometric ratio with its β-sheet.

Therapeutic use

Potential use of Lq2 is mainly in cardiovascular diseases.

References

{{Toxins Neurotoxins Ion channel toxins Scorpion toxins