S-Conotoxin RVIIIA: A Structurally Unique Conotoxin That Broadly Targets Nicotinic Acetylcholine Receptors
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- 作者：Russell W. Teichert ; Elsie C. Jimenez ; and Baldomero M. Olivera
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：May 31, 2005
- 年：2005
- 卷：44
- 期：21
- 页码：7897 - 7902
- 全文大小：102K
- 年卷期：v.44,no.21(May 31, 2005)
- ISSN：1520-4995
文摘
We report the purification and characterization of a new conotoxin from the venom of Conusradiatus. The peptide, 
chars/alpha.gif" BORDER=0>S-conotoxin RVIIIA (chars/alpha.gif" BORDER=0>S-RVIIIA), is biochemically unique with respect to itsamino acid sequence, post-translational modification, and molecular targets. In comparison to other nicotinicantagonists from Conus venoms, chars/alpha.gif" BORDER=0>S-RVIIIA exhibits an unusually broad targeting specificity for nicotinicacetylcholine receptor (nAChR) subtypes, as assayed by electrophysiology. The toxin is paralytic to miceand fish, consistent with its nearly irreversible block of the neuromuscular nAChR. Similar to otherantagonists of certain neuronal nAChRs, the toxin also elicits seizures in mice upon intracranial injection.The only previously characterized conotoxin from the S superfamily, chars/sigma.gif" BORDER=0 >-conotoxin GVIIIA, is a specificcompetitive antagonist of the 5-HT3 receptor; thus, chars/alpha.gif" BORDER=0>S-RVIIIA defines a novel family of nicotinicantagonists within the S superfamily. All previously characterized competitive conotoxin nAChR antagonistshave been members of the A superfamily of conotoxins. Our working hypothesis is that the particulargroup of fish-hunting Conus species that includes Conus radiatus uses the chars/alpha.gif" BORDER=0>S-conotoxin family to targetthe muscle nAChR and paralyze prey.
chars/alpha.gif" BORDER=0>S-conotoxin RVIIIA (chars/alpha.gif" BORDER=0>S-RVIIIA), is biochemically unique with respect to itsamino acid sequence, post-translational modification, and molecular targets. In comparison to other nicotinicantagonists from Conus venoms, chars/alpha.gif" BORDER=0>S-RVIIIA exhibits an unusually broad targeting specificity for nicotinicacetylcholine receptor (nAChR) subtypes, as assayed by electrophysiology. The toxin is paralytic to miceand fish, consistent with its nearly irreversible block of the neuromuscular nAChR. Similar to otherantagonists of certain neuronal nAChRs, the toxin also elicits seizures in mice upon intracranial injection.The only previously characterized conotoxin from the S superfamily, chars/sigma.gif" BORDER=0 >-conotoxin GVIIIA, is a specificcompetitive antagonist of the 5-HT3 receptor; thus, chars/alpha.gif" BORDER=0>S-RVIIIA defines a novel family of nicotinicantagonists within the S superfamily. All previously characterized competitive conotoxin nAChR antagonistshave been members of the A superfamily of conotoxins. Our working hypothesis is that the particulargroup of fish-hunting Conus species that includes Conus radiatus uses the chars/alpha.gif" BORDER=0>S-conotoxin family to targetthe muscle nAChR and paralyze prey.