Characterisation of a novel A-superfamily conotoxin

Wilson, David, Bansal, Paramjit S., Carter, David A., Vetter, Irina, Nicke, Annette, Dutertre, Sébastien, and Daly, Norelle (2020) Characterisation of a novel A-superfamily conotoxin. Biomedicines, 8 (5). 128.

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Abstract

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.

Item ID: 63477
Item Type: Article (Research - C1)
ISSN: 2227-9059
Keywords: conopeptide; NMR spectroscopy; disulfide framework
Copyright Information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Date Deposited: 06 Aug 2020 06:10
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060112 Structural Biology (incl Macromolecular Modelling) @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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