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Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae)
The cone snails (family Conidae) are the best known and most intensively studied venomous marine gastropods. However, of the total biodiversity of venomous marine mollusks (superfamily Conoidea, >20,000 species), cone snails comprise a minor fraction. The venoms of the family Drilliidae, a highly...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472735/ https://www.ncbi.nlm.nih.gov/pubmed/32784699 http://dx.doi.org/10.3390/toxins12080508 |
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author | Chua, Victor M. Gajewiak, Joanna Watkins, Maren Espino, Samuel S. Ramiro, Iris Bea L. Omaga, Carla A. Imperial, Julita S. Carpio, Louie Paolo D. Fedosov, Alexander Safavi-Hemami, Helena Salvador-Reyes, Lilibeth A. Olivera, Baldomero M. Concepcion, Gisela P. |
author_facet | Chua, Victor M. Gajewiak, Joanna Watkins, Maren Espino, Samuel S. Ramiro, Iris Bea L. Omaga, Carla A. Imperial, Julita S. Carpio, Louie Paolo D. Fedosov, Alexander Safavi-Hemami, Helena Salvador-Reyes, Lilibeth A. Olivera, Baldomero M. Concepcion, Gisela P. |
author_sort | Chua, Victor M. |
collection | PubMed |
description | The cone snails (family Conidae) are the best known and most intensively studied venomous marine gastropods. However, of the total biodiversity of venomous marine mollusks (superfamily Conoidea, >20,000 species), cone snails comprise a minor fraction. The venoms of the family Drilliidae, a highly diversified family in Conoidea, have not previously been investigated. In this report, we provide the first biochemical characterization of a component in a Drilliidae venom and define a gene superfamily of venom peptides. A bioactive peptide, cdg14a, was purified from the venom of Clavus davidgilmouri Fedosov and Puillandre, 2020. The peptide is small (23 amino acids), disulfide-rich (4 cysteine residues) and belongs to the J-like drillipeptide gene superfamily. Other members of this superfamily share a conserved signal sequence and the same arrangement of cysteine residues in their predicted mature peptide sequences. The cdg14a peptide was chemically synthesized in its bioactive form. It elicited scratching and hyperactivity, followed by a paw-thumping phenotype in mice. Using the Constellation Pharmacology platform, the cdg14a drillipeptide was shown to cause increased excitability in a majority of non-peptidergic nociceptors, but did not affect other subclasses of dorsal root ganglion (DRG) neurons. This suggests that the cdg14a drillipeptide may be blocking a specific molecular isoform of potassium channels. The potency and selectivity of this biochemically characterized drillipeptide suggest that the venoms of the Drilliidae are a rich source of novel and selective ligands for ion channels and other important signaling molecules in the nervous system. |
format | Online Article Text |
id | pubmed-7472735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74727352020-09-17 Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae) Chua, Victor M. Gajewiak, Joanna Watkins, Maren Espino, Samuel S. Ramiro, Iris Bea L. Omaga, Carla A. Imperial, Julita S. Carpio, Louie Paolo D. Fedosov, Alexander Safavi-Hemami, Helena Salvador-Reyes, Lilibeth A. Olivera, Baldomero M. Concepcion, Gisela P. Toxins (Basel) Article The cone snails (family Conidae) are the best known and most intensively studied venomous marine gastropods. However, of the total biodiversity of venomous marine mollusks (superfamily Conoidea, >20,000 species), cone snails comprise a minor fraction. The venoms of the family Drilliidae, a highly diversified family in Conoidea, have not previously been investigated. In this report, we provide the first biochemical characterization of a component in a Drilliidae venom and define a gene superfamily of venom peptides. A bioactive peptide, cdg14a, was purified from the venom of Clavus davidgilmouri Fedosov and Puillandre, 2020. The peptide is small (23 amino acids), disulfide-rich (4 cysteine residues) and belongs to the J-like drillipeptide gene superfamily. Other members of this superfamily share a conserved signal sequence and the same arrangement of cysteine residues in their predicted mature peptide sequences. The cdg14a peptide was chemically synthesized in its bioactive form. It elicited scratching and hyperactivity, followed by a paw-thumping phenotype in mice. Using the Constellation Pharmacology platform, the cdg14a drillipeptide was shown to cause increased excitability in a majority of non-peptidergic nociceptors, but did not affect other subclasses of dorsal root ganglion (DRG) neurons. This suggests that the cdg14a drillipeptide may be blocking a specific molecular isoform of potassium channels. The potency and selectivity of this biochemically characterized drillipeptide suggest that the venoms of the Drilliidae are a rich source of novel and selective ligands for ion channels and other important signaling molecules in the nervous system. MDPI 2020-08-07 /pmc/articles/PMC7472735/ /pubmed/32784699 http://dx.doi.org/10.3390/toxins12080508 Text en © 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chua, Victor M. Gajewiak, Joanna Watkins, Maren Espino, Samuel S. Ramiro, Iris Bea L. Omaga, Carla A. Imperial, Julita S. Carpio, Louie Paolo D. Fedosov, Alexander Safavi-Hemami, Helena Salvador-Reyes, Lilibeth A. Olivera, Baldomero M. Concepcion, Gisela P. Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae) |
title | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae) |
title_full | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae) |
title_fullStr | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae) |
title_full_unstemmed | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae) |
title_short | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae) |
title_sort | purification and characterization of the pink-floyd drillipeptide, a bioactive venom peptide from clavus davidgilmouri (gastropoda: conoidea: drilliidae) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472735/ https://www.ncbi.nlm.nih.gov/pubmed/32784699 http://dx.doi.org/10.3390/toxins12080508 |
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