Characterisation of a novel A-superfamily conotoxin
Journal Publication ResearchOnline@JCUAbstract
Conopeptides belonging to the A-superfamily from the venomous molluscs, Conus, are typically α-conotoxins. The α-conotoxins are of interest as therapeutic leads and pharmacological tools due to their selectivity and potency at nicotinic acetylcholine receptor (nAChR) subtypes. Structurally, the α-conotoxins have a consensus fold containing two conserved disulfide bonds that define the two-loop framework and brace a helical region. Here we report on a novel α-conotoxin Pl168, identified from the transcriptome of Conus planorbis, which has an unusual 4/8 loop framework. Unexpectedly, NMR determination of its three-dimensional structure reveals a new structural type of A-superfamily conotoxins with a different disulfide-stabilized fold, despite containing the conserved cysteine framework and disulfide connectivity of classical α-conotoxins. The peptide did not demonstrate activity on a range of nAChRs, or Ca2+ and Na+ channels suggesting that it might represent a new pharmacological class of conotoxins.
Journal
Biomedicines
Publication Name
N/A
Volume
8
ISBN/ISSN
2227-9059
Edition
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Issue
5
Pages Count
10
Location
N/A
Publisher
MDPI
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Publisher Location
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Date
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EISSN
N/A
DOI
10.3390/biomedicines8050128