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Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins

Elevenins are peptides found in a range of organisms, including arthropods, annelids, nematodes, and molluscs. They consist of 17 to 19 amino acid residues with a single conserved disulfide bond. The subject of this study, elevenin-Vc1, was first identified in the venom of the cone snail Conus victo...

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Autores principales: Krishnarjuna, Bankala, Sunanda, Punnepalli, Seow, Jeffrey, Tae, Han-Shen, Robinson, Samuel D., Belgi, Alessia, Robinson, Andrea J., Safavi-Hemami, Helena, Adams, David J., Norton, Raymond S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963005/
https://www.ncbi.nlm.nih.gov/pubmed/36827123
http://dx.doi.org/10.3390/md21020081
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author Krishnarjuna, Bankala
Sunanda, Punnepalli
Seow, Jeffrey
Tae, Han-Shen
Robinson, Samuel D.
Belgi, Alessia
Robinson, Andrea J.
Safavi-Hemami, Helena
Adams, David J.
Norton, Raymond S.
author_facet Krishnarjuna, Bankala
Sunanda, Punnepalli
Seow, Jeffrey
Tae, Han-Shen
Robinson, Samuel D.
Belgi, Alessia
Robinson, Andrea J.
Safavi-Hemami, Helena
Adams, David J.
Norton, Raymond S.
author_sort Krishnarjuna, Bankala
collection PubMed
description Elevenins are peptides found in a range of organisms, including arthropods, annelids, nematodes, and molluscs. They consist of 17 to 19 amino acid residues with a single conserved disulfide bond. The subject of this study, elevenin-Vc1, was first identified in the venom of the cone snail Conus victoriae (Gen. Comp. Endocrinol. 2017, 244, 11–18). Although numerous elevenin sequences have been reported, their physiological function is unclear, and no structural information is available. Upon intracranial injection in mice, elevenin-Vc1 induced hyperactivity at doses of 5 or 10 nmol. The structure of elevenin-Vc1, determined using nuclear magnetic resonance spectroscopy, consists of a short helix and a bend region stabilised by the single disulfide bond. The elevenin-Vc1 structural fold is similar to that of α-conotoxins such as α-RgIA and α-ImI, which are also found in the venoms of cone snails and are antagonists at specific subtypes of nicotinic acetylcholine receptors (nAChRs). In an attempt to mimic the functional motif, Asp-Pro-Arg, of α-RgIA and α-ImI, we synthesised an analogue, designated elevenin-Vc1-DPR. However, neither elevenin-Vc1 nor the analogue was active at six different human nAChR subtypes (α1β1εδ, α3β2, α3β4, α4β2, α7, and α9α10) at 1 µM concentrations.
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spelling pubmed-99630052023-02-26 Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins Krishnarjuna, Bankala Sunanda, Punnepalli Seow, Jeffrey Tae, Han-Shen Robinson, Samuel D. Belgi, Alessia Robinson, Andrea J. Safavi-Hemami, Helena Adams, David J. Norton, Raymond S. Mar Drugs Article Elevenins are peptides found in a range of organisms, including arthropods, annelids, nematodes, and molluscs. They consist of 17 to 19 amino acid residues with a single conserved disulfide bond. The subject of this study, elevenin-Vc1, was first identified in the venom of the cone snail Conus victoriae (Gen. Comp. Endocrinol. 2017, 244, 11–18). Although numerous elevenin sequences have been reported, their physiological function is unclear, and no structural information is available. Upon intracranial injection in mice, elevenin-Vc1 induced hyperactivity at doses of 5 or 10 nmol. The structure of elevenin-Vc1, determined using nuclear magnetic resonance spectroscopy, consists of a short helix and a bend region stabilised by the single disulfide bond. The elevenin-Vc1 structural fold is similar to that of α-conotoxins such as α-RgIA and α-ImI, which are also found in the venoms of cone snails and are antagonists at specific subtypes of nicotinic acetylcholine receptors (nAChRs). In an attempt to mimic the functional motif, Asp-Pro-Arg, of α-RgIA and α-ImI, we synthesised an analogue, designated elevenin-Vc1-DPR. However, neither elevenin-Vc1 nor the analogue was active at six different human nAChR subtypes (α1β1εδ, α3β2, α3β4, α4β2, α7, and α9α10) at 1 µM concentrations. MDPI 2023-01-25 /pmc/articles/PMC9963005/ /pubmed/36827123 http://dx.doi.org/10.3390/md21020081 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krishnarjuna, Bankala
Sunanda, Punnepalli
Seow, Jeffrey
Tae, Han-Shen
Robinson, Samuel D.
Belgi, Alessia
Robinson, Andrea J.
Safavi-Hemami, Helena
Adams, David J.
Norton, Raymond S.
Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins
title Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins
title_full Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins
title_fullStr Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins
title_full_unstemmed Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins
title_short Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of α-Conotoxins
title_sort characterisation of elevenin-vc1 from the venom of conus victoriae: a structural analogue of α-conotoxins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963005/
https://www.ncbi.nlm.nih.gov/pubmed/36827123
http://dx.doi.org/10.3390/md21020081
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