# Towards Understanding the Function of Aegerolysins
###### Abstract  
Aegerolysins are remarkable proteins. They are distributed over the tree of life, being relatively widespread in bacteria and fungi, but also present in some insects, plants, protozoa, and viruses. Despite their abundance in cells of certain developmental stages and their presence in secretomes, only a few aegerolysins have been studied in detail. Their function, in particular, is intriguing. Here, we summarize previously published findings on the distribution, molecular interactions, and function of these versatile aegerolysis. They have very diverse protein sequences but a common fold. The machine learning approach of the AlphaFold2 algorithm, which incorporates physical and biological knowledge of protein structures and multisequence alignments, provides us new insights into the aegerolysins and their pore-forming partners, complemented by additional genomic support. We hypothesize that aegerolysins are involved in the mechanisms of competitive exclusion in the niche.  
aegerolysins; AlphaFold structure modeling; bacteria; competitive exclusion; fungi; insecticidal; lipid binding; lifestyle; membrane-attack complex/perforin domain (MACPF); pore forming proteins +
Footnote †: journal: _Toxins_  
0000-0002-3000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-00000-0000-00000-00000-00000-00000-000  
Despite the limited scientific knowledge about the function of aegyptis, several potential applications are already emerging. Most commonly, some fungal aegyptis serve as probes for the detection, labeling, and imaging of specific membrane lipids, lipid rafts, cancer cells, invertebrates, or parasites [4; 6; 7; 8; 9; 10; 11]. In high concentrations, they can induce both artificial lipid vesicles as well as live cells, such as blood cells or neuroblastoma cells, to bend and bud [10]. A role of some aegyptis in combating obesity and related metabolic disorders has been recognized [10]. Their genes and expression may serve as markers for the progression of fruiting body differentiation during mushrooms cultivation [10] or as biomarkers to detect fungal exposure and progression of infectious disease [3; 4]. In addition, antibodies produced against aegyptis can serve as immuno-diagnostic tools [4]. Due to their variable sequence, aegyptis serve as tools to identify of fungal phytopathogen isolates compared to some closely related species where the internal transcribed spacer barcoding method has failed [4]. Strong promoters regulating aegyptis genes can promote the secretion of heterologous proteins from fungi in concomitant multi-gene expression [4]. Certain aegyptis that combine with larger protein partners to form pore-forming complexes can be used to selectively eliminate insect pests [4; 10] or to treat certain types of cancer cells [4; 10].  
Currently, a total of 2303 sequenced genomes of fungal species are deposited in the largest public database of fungal genomes [12]. Aegerolysins are encoded in the genomes of Dikarya fungi but are absent in some clades, e.g., Saccharomyces [4]. Fungal genomes contain 949 protein sequences with the recognized aegypti domain PF06355 [12]. In 31,332 genomes in a bacterial database, there were 169 hits for aegerolysins [13]. Despite their presence in cells at certain developmental stages and their presence in secretomes, few aegerolysins have been studied in detail.  
Here we provide a complete overview of the lifestyles of organisms (fungi, bacteria, insects, and viruses) in which aegyptis have been identified not only by genome sequencing, but also with at least some previously described functional properties. Their putative structures were predicted using the recently introduced successful prediction tool AlphaFold2 to further improve the knowledge of their function [14]. The presence of putative bicomponent partner proteins or additional aegerolysin gene copies was also investigated.