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

Abstract

Many of the small, cysteine‐rich ion‐channel modulatory peptides found in Cnidaria are distantly related to vertebrate defensins (of the trans‐defensin superfamily). Transcriptomic and proteomic studies of the endemic Australian speckled sea anemone (Oulactis sp.) yielded homologous peptides to known defensin sequences. We extended these data using existing and custom‐built hidden Markov models to extract defensin‐like families from the transcriptomes of seven endemic Australian cnidarian species. Newly sequenced transcriptomes include three species of Actiniaria (true sea anemones); the speckled anemone (Oulactis sp.), Oulactis muscosa, Dofleinia cf. armata and a species of Corallimorpharia, Rhodactis sp. We analyzed these novel defensin‐like sequences along with published homologues to study the evolution of their physico‐chemical properties in vertebrate and invertebrate fauna. The cnidarian trans‐defensins form a distinct cluster within the chemical space of the superfamily, with a unique set of motifs and biophysical properties. This cluster contains identifiable subgroups, whose distribution in chemical space also correlates with the divergent evolution of their structures. These sequences, currently restricted to cnidarians, form an evolutionarily distinct clade within the trans‐defensin superfamily.

Magnificamide, a β-Defensin-Like Peptide from the Mucus of the Sea Anemone Heteractis magnifica, Is a Strong Inhibitor of Mammalian α-Amylases

“…In the venoms of sea anemones, the β-defensin fold is widely recruited to create toxins modulating ion channel activity, interestingly, often with little amino acid sequence identity, but with similar spatial structure. According to Mitchell and coauthors, cnidarian β-defensin-like toxins can be divided into four main groups: APETx-like, BDS-like, Nv1-like, and ShI-like [46]. Representatives of APETx-like and BDS-like groups interact with ASICs, hERG, voltage-gated sodium, and potassium ion channels [33,47,48,49].…”

The Dichotomous Responses Driven by β-Defensins

“…The cis-defensin superfamily (present in insects, fungi and plants), has the central beta-strand stabilised by disulphide bridges, connected to the same alpha-helix in the "cis" orientation. This is in contrast to the vertebrate (and some invertebrate) defensins, in which the central beta strand has disulphide bridges that stabilise structures in non-cis or "trans" orientations (3,4). Both cis and trans families have undergone rapid expansion and evolutionary change to reveal a repertoire of diverse functions that are only recently becoming clear (5).…”

New Insights into the Type II Toxins from the Sea Anemone Heteractis crispa

“…The vast majority of experiments elucidating the effects of sea anemone toxins on Na V currents were carried out using the type I toxins: ApA and ApB from Anthopleura xanthogrammica [11,12], APE1-APE5 from Anthopleura elegantissima [13]. At the same time, recent investigations of the diversity and functional consequences of type I toxins [14] underscore the substantial difference in the physico-chemical properties and spatial structure of the type I and type II toxins [15].…”

“…Toxicity in both mammals and crustaceans has been shown for the type I and II toxins [8][9][10].The vast majority of experiments elucidating the effects of sea anemone toxins on Na V currents were carried out using the type I toxins: ApA and ApB from Anthopleura xanthogrammica [11,12], APE1-APE5 from Anthopleura elegantissima [13]. At the same time, recent investigations of the diversity and functional consequences of type I toxins [14] underscore the substantial difference in the physico-chemical properties and spatial structure of the type I and type II toxins [15].The structural type II includes ShI from Stichodactyla helianthus [9], RpI-RpIV from Heteractis magnifica (= Radianthus paumotensis) [8], and RTX-I-RTX-V from Heteractis crispa (= Radianthus macrodactylus) [10,[16][17][18]. Electrophysiological studies of ShI and RpI-RpIV [8,19] allowed the determination of a common mechanism of their action on Na V , but not a pharmacological profile.…”