Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from <i>Clavus davidgilmouri</i> (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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/8/508 |
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| author | Victor M. Chua Joanna Gajewiak Maren Watkins Samuel S. Espino Iris Bea L. Ramiro Carla A. Omaga Julita S. Imperial Louie Paolo D. Carpio Alexander Fedosov Helena Safavi-Hemami Lilibeth A. Salvador-Reyes Baldomero M. Olivera Gisela P. Concepcion |
| author_facet | Victor M. Chua Joanna Gajewiak Maren Watkins Samuel S. Espino Iris Bea L. Ramiro Carla A. Omaga Julita S. Imperial Louie Paolo D. Carpio Alexander Fedosov Helena Safavi-Hemami Lilibeth A. Salvador-Reyes Baldomero M. Olivera Gisela P. Concepcion |
| author_sort | Victor M. Chua |
| collection | DOAJ |
| 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 <i>Clavus davidgilmouri</i> 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. |
| first_indexed | 2024-03-10T17:48:00Z |
| format | Article |
| id | doaj.art-86f797d62fa14a1784a27bff9dda1c29 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T17:48:00Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-86f797d62fa14a1784a27bff9dda1c292023-11-20T09:26:54ZengMDPI AGToxins2072-66512020-08-0112850810.3390/toxins12080508Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from <i>Clavus davidgilmouri</i> (Gastropoda: Conoidea: Drilliidae)Victor M. Chua0Joanna Gajewiak1Maren Watkins2Samuel S. Espino3Iris Bea L. Ramiro4Carla A. Omaga5Julita S. Imperial6Louie Paolo D. Carpio7Alexander Fedosov8Helena Safavi-Hemami9Lilibeth A. Salvador-Reyes10Baldomero M. Olivera11Gisela P. Concepcion12The Marine Science Institute, University of the Philippines, Diliman, Quezon City 1101, PhilippinesSchool of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USASchool of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USASchool of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USAThe Marine Science Institute, University of the Philippines, Diliman, Quezon City 1101, PhilippinesThe Marine Science Institute, University of the Philippines, Diliman, Quezon City 1101, PhilippinesSchool of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USAThe Marine Science Institute, University of the Philippines, Diliman, Quezon City 1101, PhilippinesSeverstov Institute of Ecology and Evolution, Russian Academy of Sciences, Leninsky prospect 33, Moscow 119071, RussiaSchool of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USAThe Marine Science Institute, University of the Philippines, Diliman, Quezon City 1101, PhilippinesSchool of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USAThe Marine Science Institute, University of the Philippines, Diliman, Quezon City 1101, PhilippinesThe 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 <i>Clavus davidgilmouri</i> 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.https://www.mdpi.com/2072-6651/12/8/508venom<i>Clavus</i>Drilliidaedrillipeptide |
| spellingShingle | Victor M. Chua Joanna Gajewiak Maren Watkins Samuel S. Espino Iris Bea L. Ramiro Carla A. Omaga Julita S. Imperial Louie Paolo D. Carpio Alexander Fedosov Helena Safavi-Hemami Lilibeth A. Salvador-Reyes Baldomero M. Olivera Gisela P. Concepcion Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from <i>Clavus davidgilmouri</i> (Gastropoda: Conoidea: Drilliidae) Toxins venom <i>Clavus</i> Drilliidae drillipeptide |
| title | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from <i>Clavus davidgilmouri</i> (Gastropoda: Conoidea: Drilliidae) |
| title_full | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from <i>Clavus davidgilmouri</i> (Gastropoda: Conoidea: Drilliidae) |
| title_fullStr | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from <i>Clavus davidgilmouri</i> (Gastropoda: Conoidea: Drilliidae) |
| title_full_unstemmed | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from <i>Clavus davidgilmouri</i> (Gastropoda: Conoidea: Drilliidae) |
| title_short | Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from <i>Clavus davidgilmouri</i> (Gastropoda: Conoidea: Drilliidae) |
| title_sort | purification and characterization of the pink floyd drillipeptide a bioactive venom peptide from i clavus davidgilmouri i gastropoda conoidea drilliidae |
| topic | venom <i>Clavus</i> Drilliidae drillipeptide |
| url | https://www.mdpi.com/2072-6651/12/8/508 |
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