Phylogenetic distribution, functional epitopes and evolution of the CSαβ superfamily

Abstract

A superfamily of proteins often conserves a common structural scaffold but develops diverse biochemical and biological functions during evolution. The understanding of evolutionary mechanisms responsible for this diversity is of fundamental importance not only in structural genomics but also in nature-guided drug design. A superfamily of peptides with a conserved CSalphabeta structural motif provides a considerably intriguing example to approach such an issue. The peptides from this superfamily have wide origins, ranging from plants to animals, and exhibit diverse biological activities, varying from a sweet-tasting protein to antibacterial defensins and animal toxins targeting ion channels. This review describes the phylogenetic distribution and structural classifi cation of this unique scaffold and provides new insights into its functional diversity from the perspective of sequence, structure and evolution.

Nematode-derived drosomycin-type antifungal peptides provide evidence for plant-to-ecdysozoan horizontal transfer of a disease resistance gene

“…Experimental deletion of the NC-domain of a scorpion toxin resulted in antifungal ability of the toxin 25 , whereas the addition of the NC-domain of a toxin on the drosomycin scaffold led to a neurotoxin targeting rat sodium channels 26 . These data provide convincing functional evidence in favour of evolutionary link between drosomycins and scorpion sodium channel toxins, and present an example of divergent evolution occurring in a specific arthropod lineage, in which a DTAFP evolved into a neurotoxin [24][25][26] . The insertion of a small fragment, as the N-turn of the scorpion toxins, in the N-terminal region of a DTAFP is also seen in mehamycin (Fig.…”

“…Similarly, drosomycin has been found to gain ability in interacting with the fly voltage-gated sodium channel, possibly acting as a neuropeptide 25 . In C. remanei, cremycin-15 has evolved antibacterial activity described here, while scorpion venom-derived DTAFPs have switched their targets from fungi to animal sodium channels [24][25][26] . All these observations suggest that the gene can be fixed only in organisms where it developed important functions following gene duplication and speciation.…”

“…7a). They have an unusual structure that is composed of a conserved core folding into a drosomycin-like scaffold and an NC-domain comprising the N-terminal turn (N-turn) and C-tail 24 (Fig. 7b).…”

Molecular diversity and evolution of defensins in the manila clam Ruditapes philippinarum

“…Due to their direct interaction with altered/new pathogens, AMPs exhibit an extraordinary diversity in their biochemical and biological functions. It has been reported that positive Darwinian selection was the major driving force in the generation of diverse AMPs [47].…”

“…Zhu et al [47] also reported that many members of the CS-ab superfamily exhibited molecular diversity and diverse biological functions, and suggested that positive Darwinian selection is the major driving force in generating such diversity. The direct involvement of these peptides with the altered pathogens in a changing environment is probably the cause of such adaptive molecular evolution of these AMPs [25].…”