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Characterisation of a Novel A-Superfamily Conotoxin.

ABSTRACT: Conopeptides belonging to the A-superfamily from the venomous molluscs, Conus, are typically ?-conotoxins. The ?-conotoxins are of interest as therapeutic leads and pharmacological tools due to their selectivity and potency at nicotinic acetylcholine receptor (nAChR) subtypes. Structurally, the ?-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 ?-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 ?-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.

SUBMITTER: Wilson DT 

PROVIDER: S-EPMC7277881 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Characterisation of a Novel A-Superfamily Conotoxin.

Wilson David T DT   Bansal Paramjit S PS   Carter David A DA   Vetter Irina I   Nicke Annette A   Dutertre Sébastien S   Daly Norelle L NL  

Biomedicines 20200520 5

Conopeptides belonging to the A-superfamily from the venomous molluscs, <i>Conus</i>, 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 fr  ...[more]

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