C-Conotoxin PrXA: A New Family of Nicotinic Acetylcholine Receptor Antagonists
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- 作者：Elsie C. Jimenez ; Baldomero M. Olivera ; Russell W. Teichert
- 刊名：Biochemistry
- 出版年：2007
- 出版时间：July 31, 2007
- 年：2007
- 卷：46
- 期：30
- 页码：8717 - 8724
- 全文大小：272K
- 年卷期：v.46,no.30(July 31, 2007)
- ISSN：1520-4995
文摘
We have purified a novel paralytic peptide with 32 AA and a single disulfide bond from thevenom of Conus parius, a fish-hunting species. The peptide has the following sequence: TYGIYDAKPOFSCAGLRGGCVLPONLROKFKE-NH2, where O is 4-trans-hydroxyproline. The peptide, designated
C-conotoxin PrXA (C-PrXA), is the defining member of a new, structurally distinct family of Conuspeptides. The peptide is a competitive nAChR antagonist; all previously characterized conotoxins thatcompetitively antagonize nAChRs are structurally and genetically unrelated. (Most belong to the - andA-conotoxin families.) When administered to mice and fish in vivo, C-PrXA caused paralysis anddeath. In electrophysiological assays, C-PrXA potently antagonized mouse muscle nicotinic acetylcholinereceptors (nAChRs), with IC50 values of 1.8 and 3.0 nM for the adult (1
1
subunits) and fetal (11
subunits) muscle nAChR subtypes, respectively. When tested on a variety of ligand-gated and voltage-gated ion channels, C-PrXA proved to be a highly specific inhibitor of the neuromuscular nAChR. Thepeptide competes with -bungarotoxin for binding at the / and / subunit interfaces of the nAChR,with higher affinity for the / subunit interface. C-PrXA is strikingly different from the manyconopeptides shown to be nicotinic antagonists; it is most similar in its general biochemical features tothe snake toxins known as Waglerins.
C-conotoxin PrXA (C-PrXA), is the defining member of a new, structurally distinct family of Conuspeptides. The peptide is a competitive nAChR antagonist; all previously characterized conotoxins thatcompetitively antagonize nAChRs are structurally and genetically unrelated. (Most belong to the - andA-conotoxin families.) When administered to mice and fish in vivo, C-PrXA caused paralysis anddeath. In electrophysiological assays, C-PrXA potently antagonized mouse muscle nicotinic acetylcholinereceptors (nAChRs), with IC50 values of 1.8 and 3.0 nM for the adult (11 subunits) and fetal (11subunits) muscle nAChR subtypes, respectively. When tested on a variety of ligand-gated and voltage-gated ion channels, C-PrXA proved to be a highly specific inhibitor of the neuromuscular nAChR. Thepeptide competes with -bungarotoxin for binding at the / and / subunit interfaces of the nAChR,with higher affinity for the / subunit interface. C-PrXA is strikingly different from the manyconopeptides shown to be nicotinic antagonists; it is most similar in its general biochemical features tothe snake toxins known as Waglerins.