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Article Dans Une Revue Biomedicines Année : 2020

Characterisation of a Novel A-Superfamily Conotoxin

Résumé

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.

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Chimie organique
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Dates et versions

hal-03031288 , version 1 (25-05-2021)

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David Wilson, Paramjit Bansal, David Carter, Irina Vetter, Annette Nicke, et al.. Characterisation of a Novel A-Superfamily Conotoxin. Biomedicines, 2020, 8 (5), pp.128. ⟨10.3390/biomedicines8050128⟩. ⟨hal-03031288⟩
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