Characterisation of a Novel A-Superfamily Conotoxin
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. Str...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/5/128 |
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| author | David T. Wilson Paramjit S. Bansal David A. Carter Irina Vetter Annette Nicke Sébastien Dutertre Norelle L. Daly |
| author_facet | David T. Wilson Paramjit S. Bansal David A. Carter Irina Vetter Annette Nicke Sébastien Dutertre Norelle L. Daly |
| author_sort | David T. Wilson |
| collection | DOAJ |
| description | 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 from the transcriptome of <i>Conus planorbis</i>, 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 Ca<sup>2+</sup> and Na<sup>+</sup> channels suggesting that it might represent a new pharmacological class of conotoxins. |
| first_indexed | 2024-03-10T19:43:23Z |
| format | Article |
| id | doaj.art-039754bf867642f2b168c1a4f313cbaf |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T19:43:23Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-039754bf867642f2b168c1a4f313cbaf2023-11-20T01:02:02ZengMDPI AGBiomedicines2227-90592020-05-018512810.3390/biomedicines8050128Characterisation of a Novel A-Superfamily ConotoxinDavid T. Wilson0Paramjit S. Bansal1David A. Carter2Irina Vetter3Annette Nicke4Sébastien Dutertre5Norelle L. Daly6Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD 4878, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD 4878, AustraliaCentre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaCentre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, LMU Munich, Nußbaumstraße 26, 80336 Munich, GermanyInstitut des Biomolécules Max Mousseron, UMR 5247, Université de Montpellier, CNRS, 34095 Montpellier, FranceCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD 4878, AustraliaConopeptides 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 from the transcriptome of <i>Conus planorbis</i>, 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 Ca<sup>2+</sup> and Na<sup>+</sup> channels suggesting that it might represent a new pharmacological class of conotoxins.https://www.mdpi.com/2227-9059/8/5/128conopeptideNMR spectroscopydisulfide framework |
| spellingShingle | David T. Wilson Paramjit S. Bansal David A. Carter Irina Vetter Annette Nicke Sébastien Dutertre Norelle L. Daly Characterisation of a Novel A-Superfamily Conotoxin Biomedicines conopeptide NMR spectroscopy disulfide framework |
| title | Characterisation of a Novel A-Superfamily Conotoxin |
| title_full | Characterisation of a Novel A-Superfamily Conotoxin |
| title_fullStr | Characterisation of a Novel A-Superfamily Conotoxin |
| title_full_unstemmed | Characterisation of a Novel A-Superfamily Conotoxin |
| title_short | Characterisation of a Novel A-Superfamily Conotoxin |
| title_sort | characterisation of a novel a superfamily conotoxin |
| topic | conopeptide NMR spectroscopy disulfide framework |
| url | https://www.mdpi.com/2227-9059/8/5/128 |
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