TY - JOUR

T1 - Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide fromClavus davidgilmouri (Gastropoda: Conoidea: Drilliidae) 

AU - Chua, Victor M.

AU - Gajewiak, Joanna

AU - Watkins, Maren

AU - Espino, Samuel S.

AU - Ramiro, Iris Bea L.

AU - Omaga, Carla A.

AU - Imperial, Julita S.

AU - Carpio, Louie Paolo D.

AU - Fedosov, Alexander

AU - Safavi-Hemami, Helena

AU - Salvador-Reyes, Lilibeth A.

AU - Olivera, Baldomero M.

AU - Concepcion, Gisela P.

PY - 2020

Y1 - 2020

N2 - 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 ofClavus davidgilmouriFedosov 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.

AB - 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 ofClavus davidgilmouriFedosov 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.

KW - venom

KW - Clavus

KW - Drilliidae

KW - drillipeptide

KW - CONSTELLATION PHARMACOLOGY

KW - MOLECULAR PHYLOGENY

KW - SUPERFAMILY

KW - CHANNEL

KW - TOXINS

U2 - 10.3390/toxins12080508

DO - 10.3390/toxins12080508

M3 - Journal article

C2 - 32784699

VL - 12

JO - Toxins

JF - Toxins

SN - 2072-6651

IS - 8

M1 - 508

ER -