αC-Conotoxin PrXA (AlphaC-PrXA) is a conotoxin that was originally isolated from the venom of the fish-hunting Conus parius. αC-Conotoxin PrXA is a highly specific inhibitor of the neuromuscular nAChR. It potently antagonizes mouse muscle adult α1/β1/ε/δ nAChR subunits (IC50 = 1.8 nM) as well as fetal mouse muscle α1/β1/γ/δ nAChR subunits (IC50 = 3 nM). αC-Conotoxin PrXA competes with α-bungarotoxin for binding at the α/δ and α/γ nAChR subunit interfaces (with higher affinity however for the α/δ subunit interface such as α-conotoxin GI and α-conotoxin MI). The 3D structure of αC-Conotoxin PrXA is different from other conotoxins that target nAChR and it is most similar to Waglerin-1, a nAChR blocker isolated from a snake venom. αC-Conotoxin PrXA is a useful tool for investigating the structure and physiological role of nAChRs.
Description:
AA sequence: Thr-Tyr-Gly-Ile-Tyr-Asp-Ala-Lys-Pro-Hyp-Phe-Ser-Cys13-Ala-Gly-Leu-Arg-Gly-Gly-Cys20-Val-Leu-Pro-Hyp-Asn-Leu-Arg-Hyp-Lys-Phe-Lys-Glu-NH2
Disulfide bonds: Cys13-Cys20
Length (aa): 32
Formula: C160H249N43O44S2
Molecular Weight: 3541.1 Da
Appearance: White lyophilized solid
Solubility: water or saline buffer
CAS number: not available
Source: Synthetic
Purity rate: > 95 %
Reference:
Diversity of Conus peptides that target the nicotinic acetylcholine receptors
AlphaC-conotoxin PrXA: a new family of nicotinic acetylcholine receptor antagonists. Biochemistry
We have purified a novel paralytic peptide with 32 AA and a single disulfide bond from the venom of Conus parius, a fish-hunting species. The peptide has the following sequence: TYGIYDAKPOFSCAGLRGGCVLPONLROKFKE-NH2, where O is 4-trans-hydroxyproline. The peptide, designated alphaC-conotoxin PrXA (alphaC-PrXA), is the defining member of a new, structurally distinct family of Conus peptides. The peptide is a competitive nAChR antagonist; all previously characterized conotoxins that competitively antagonize nAChRs are structurally and genetically unrelated. (Most belong to the alpha- and alphaA-conotoxin families.) When administered to mice and fish in vivo, alphaC-PrXA caused paralysis and death. In electrophysiological assays, alphaC-PrXA potently antagonized mouse muscle nicotinic acetylcholine receptors (nAChRs), with IC50 values of 1.8 and 3.0 nM for the adult (alpha1beta1 epsilondelta subunits) and fetal (alpha1beta1 gammadelta subunits) muscle nAChR subtypes, respectively. When tested on a variety of ligand-gated and voltage-gated ion channels, alphaC-PrXA proved to be a highly specific inhibitor of the neuromuscular nAChR. The peptide competes with alpha-bungarotoxin for binding at the alpha/delta and alpha/gamma subunit interfaces of the nAChR, with higher affinity for the alpha/delta subunit interface. AlphaC-PrXA is strikingly different from the many conopeptides shown to be nicotinic antagonists; it is most similar in its general biochemical features to the snake toxins known as Waglerins.
Jimenez EC., et al. (2007) AlphaC-conotoxin PrXA: a new family of nicotinic acetylcholine receptor antagonists. Biochemistry. PMID: 17608455
