Cll2
Toxin found in scorpion venom
From Wikipedia, the free encyclopedia
Beta-toxin Cll2, shortened to Cll2, is a toxin in the venom of the Mexican scorpion species Centruroides limpidus limpidus. The toxin belongs to the β-class family of sodium channel-inhibiting scorpion toxins. It affects voltage-dependent activation, conductance and resurgent currents of voltage gated sodium channels by binding to site 4.
| Beta-toxin Cll2 (Cll2) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | |||||||
| Symbol | N/A | ||||||
| UniProt | 6876 | ||||||
| |||||||
Etymology and Source
Cll2 is named after the venom produced by the species Centruroides limpidus limpidus, a Mexican scorpion. Cll1 and Cll2 are both derived from this venom. The Centruroides limpidus limpidus species is a member of the only genus that represents a life hazard to humans in Mexico, and is mainly found in the state of Morelos.[1]
Chemistry
Cll2 belongs to the beta-type of sodium channel-inhibiting scorpion toxins. The Cll venom consists of six fractions, of which only Cll2 is lethal, amounting to ~42% of the venom. Cll2 consists of thirteen sub-fractions, of which sub-fraction 9 is the largest. The molecular weight of Cll2 is about 7600 Da. The primary structure of the Cll2 toxin (toxin II.9) is:[2]
KEGYLVNHST GCKYECFKLG DNDYCLRECK QQYGKGAGGY CYAFGCWCNH LYEQAVWPL PKKTCN
Target
Like other scorpion beta toxins (beta-ScTxs), Cll2 targets voltage-gated sodium channels (VGSCs). It specifically binds to and alters the Nav1.6 channel, as well as, but to a lesser extent, other Nav isoforms.[3] It binds to the extracellular end of the ISS4 (loop between the third and fourth segment) voltage sensor and locks it in the activated outward position.[3] This binding location is commonly referred to as VGSC site 4.[4]
Mode of action
Cll2 binding to the ISS4 shifts the voltage dependence of activation to more negative values. In addition, Cll2 shows a blocking effect on the peak transient current and it can increase the resurgent current in the Nav 1.6 isoform. The toxin can induce a resurgent current in Nav1.1 and to a lesser extent in the Nav1.2 and Nav1.4 isoforms.
Cll2 has slight differences compared to Cll1 in its mode of action. Cll2 caused a current reduction in Nav1.6 and to a lesser extent in Nav 1.1, Nav 1.4 and Nav 1.5. Cll1, on the other hand, influences the channels Nav 1.1 to Nav 1.6 all in an equal way.[3][5]
Toxicity
Treatment
The single chain variable antibody fragment (scFv) ER-5 was recently created by mutating earlier used scFVs which were used against other Mexican scorpion toxins. This scFv ER-5 was found to have a neutralizing effect on both Cll1 and Cll2.[6]