New Disulfide-Stabilized Fold Provides Sea Anemone Peptide to Exhibit Both Antimicrobial and TRPA1 Potentiating Properties

Abstract

A novel bioactive peptide named τ-AnmTx Ueq 12-1 (short name Ueq 12-1) was isolated and characterized from the sea anemone Urticina eques. Ueq 12-1 is unique among the variety of known sea anemone peptides in terms of its primary and spatial structure. It consists of 45 amino acids including 10 cysteine residues with an unusual distribution and represents a new group of sea anemone peptides. The 3D structure of Ueq 12-1, determined by NMR spectroscopy, represents a new disulfide-stabilized fold partly similar to the defensin-like fold. Ueq 12-1 showed the dual activity of both a moderate antibacterial activity against Gram-positive bacteria and a potentiating activity on the transient receptor potential ankyrin 1 (TRPA1). Ueq 12-1 is a unique peptide potentiator of the TRPA1 receptor that produces analgesic and anti-inflammatory effects in vivo. The antinociceptive properties allow us to consider Ueq 12-1 as a potential analgesic drug lead with antibacterial properties.

PHAB toxins: a unique family of predatory sea anemone toxins evolving via intra-gene concerted evolution defines a new peptide fold

“…Of these, disulfiderich peptide neurotoxins constitute the largest molecular diversity. According to the classification system proposed by Mikov and Kozlov [8], at least 17 different peptide folds have been identified in sea anemone venoms [9], although recent proteomics studies suggest that they likely contain 30 or more [10].…”

Coral Venom Toxins

“…As mentioned above, in contrast to the original suggestion, SCRiPS are not only found in corals but have been found in the sea anemones Anemonia viridis and Metridium senile (Jouiaei et al, 2015b). The toxin τ -AnmTx Ueq 12-1 isolated from the sea anemone Urticina eques also shows similarity to SCRiPs, in particular one cDNA matched the SCRiP Anthopleura elegantissima comp63456_c0_seq1 (Logashina et al, 2017). The presence of SCRiPs in corals and sea anemones suggests that these proteins evolved more than 500 million years ago, the estimated time when coral diverged from sea anemones (Shinzato et al, 2011).…”

Evolution of cnidarian trans‐defensins: Sequence, structure and exploration of chemical space

“…and Oulactis species. APETx-like b X [2][3] CXCX [12][13][14][15][16][17] CX [7--9] CX 6 CCX [0][1][2][3][4][5] Nv1-like b X [2][3] CXCX [13][14][15] CX [6--10] CX [5][6] CCX [0][1][2][3][4][5] BDS-like b X 3 CXCX [15][16][17] CX 9 CX 6 CCX [0][1][2][3][4][5] ShI-like c X 3 CXCX 20 CX 6 CX [7][8][9] CC [2][3] Helianthamide-like c X 5 the sea anemone Urticina crassicornis, located in the APETx1-like subgroup). 55 Future research will be required to determine how widespread such polyfunctionality is, and whether such peptides are enriched in particular clusters in the sequence or in the interfaces between different clusters of functions.…”

“…[11][12][13] Recently, a defensin was isolated from the venom of Urticina eques (τ-AnmTx Ueq 12-1) 14 that has a dual functionality, displaying both antibacterial activity and potentiating activity against the transient receptor potential ankyrin 1 (TRPA1). 14 Defensins do not reside only in venom; a novel β-defensin α-amylase inhibitor has been isolated from the mucus of the sea anemone Heteractis magnifica. 15 Defensin-like peptides from cnidarians thus represent a potentially valuable class of bioactive peptides.…”