Aegerolysin protein family (Pfam 06355, InterPro IPR009413) comprises low molecular (15-20 kDa), acidic, beta-structured proteins, found in several eukaryotic and bacterial taxa. The family currently contains over 350 homologues from 285 diffeerent organisms. Despite the wide distribution of aegerolysins across the kingdoms of life, and although they appear to be among major proteins secreted by the organisms that produce them, their functions and biological roles remain poorly understood.
The common feature of the aegerolysins is their ability to bind different lipids and lipid derivatives, as well as biological and artificial lipid membranes. For example, some aegerolysins can target sphingomyelin/ cholesterol membrane nanodomains. Furthermore, aegerolysins from the fungal genus Pleurotus preferentially bind to ceramide phosphoethanolamine (CPE), which is the major membrane sphingolipid of invertebrates (particularly insects and molluscs). Moreover, the genomes of some aegerolysin-producing fungi have nucleotide sequences that encode proteins with membrane-attack complex/ perforin (MACPF) domain. In the presence of a protein with a MACPF domain, fungal aegerolysins can function as bi-component lytic complexes for target cell membranes.
In order to study the biomedical or biotechnological potential of aegerolysins and aegerolysin-based binary lytic complexes, we isolated and characterized several recombinant aegerolysins (either unmodified or fused with fluorescent proteins) derived from fungi or bacteria, and evaluated their interactions with artficial and biological lipid systems, and with some target organisms.
We show that selected fluorescent fusion derivatives of fungal aegerolysins could be used as useful tools to track raft-like membrane nanodomains composed of sphingomyelin and cholesterol. Moreover, the selectivity of some aegerolysin-based cytolytic complexes for increased membrane sphingomyelin/ cholesterol contents can be exploited for selective killing of urothelial carcinoma cells. Finally, due to their specific interaction with CPE, some cytolytic complexes based on Pleurotus-derived aegerolysins could represent a novel promising class of biopesticides for controlling plant pests.