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α-Conotoxin EpI, a Novel Sulfated Peptide from Conus episcopatus That Selectively Targets Neuronal Nicotinic Acetylcholine Receptors

We have isolated and characterized α-conotoxin EpI, a novel sulfated peptide from the venom of the molluscivorous snail, Conus episcopatus . The peptide was classified as an α-conotoxin based on sequence, disulfide connectivity, and pharmacological target. EpI has homology to sequences of previous...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-06, Vol.273 (25), p.15667
Main Authors: Marion Loughnan, Trudy Bond, Anne Atkins, Javier Cuevas, David J. Adams, Natalie M. Broxton, Bruce G. Livett, John G. Down, Alun Jones, Paul F. Alewood, Richard J. Lewis
Format: Article
Language:English
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Summary:We have isolated and characterized α-conotoxin EpI, a novel sulfated peptide from the venom of the molluscivorous snail, Conus episcopatus . The peptide was classified as an α-conotoxin based on sequence, disulfide connectivity, and pharmacological target. EpI has homology to sequences of previously described α-conotoxins, particularly PnIA, PnIB, and ImI. However, EpI differs from previously reported conotoxins in that it has a sulfotyrosine residue, identified by amino acid analysis and mass spectrometry. Native EpI was shown to coelute with synthetic EpI. The peptide sequence is consistent with most, but not all, recognized criteria for predicting tyrosine sulfation sites in proteins and peptides. The activities of synthetic EpI and its unsulfated analogue [Tyr 15 ]EpI were similar. Both peptides caused competitive inhibition of nicotine action on bovine adrenal chromaffin cells (neuronal nicotinic ACh receptors) but had no effect on the rat phrenic nerve-diaphragm (muscle nicotinic ACh receptors). Both EpI and [Tyr 15 ]EpI partly inhibited acetylcholine-evoked currents in isolated parasympathetic neurons of rat intracardiac ganglia. These results indicate that EpI and [Tyr 15 ]EpI selectively inhibit α3β2 and α3β4 nicotinic acetylcholine receptors.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.25.15667