Aegerolysins: Comparison
Please note this is a comparison between Version 1 by Nada Kraševec and Version 2 by Camila Xu.

Aegerolysins are remarkable proteins. They are distributed over the tree of life, being relatively widespread in fungi and bacteria, but also present in some insects, plants, protozoa, and viruses. Their function, in particular, is intriguing. Aegerolysin proteins are involved in various interactions by recognizing a molecular receptor in the target organism. Despite their abundance in cells of certain developmental stages and their presence in secretomes, only a few aegerolysins have been studied in detail. Formation of pores with various larger non-aegerolysin-like protein partners is one of the possible responses of the aegerolysin-producing organism in competitive exclusion of other organisms from the ecological niche.

  • aegerolysins
  • bacteria
  • fungi
  • insecticidal
  • lipid binding
  • lifestyle
  • membrane-attack complex/perforin domain (MACPF)
  • pore forming proteins

1. Introduction

The aegerolysin family (Pfam 06355) is a lesser-known protein family that has received increasing attention in recent years. The aegerolysin family consists of proteins that are biochemically characterized as β-structured proteins and share some common features: similar small molecular weights (15–20 kDa), low isoelectric points, and stability in a wide pH range [1]. Because they are non-core proteins, without a member of this protein family in each of the sequenced fungi, their distribution among fungal species is inconsistent, and different numbers of homologs have been reported for species within the same genus [2][3][4][2,3,4]. They are not only relatively widespread in fungi and bacteria, but also identified in few plants, protozoa, viruses, and insects [1][2][1,2].
In recent years, several reviews of this protein family have been published, but none of them included data on the ecology of the organisms producing them. In particular, their function is enigmatic, although some authors suggest a role in the development of the organism [1][2][3][1,2,3]. However, some of them function as two-component cytolysins that exhibit membrane permeabilization activity together with another non-aegerolysin-like protein [2][5][2,5]; these act together to perforate natural and artificial lipid membranes [1][2][5][1,2,5]. The aegerolysin-like proteins provide membrane lipid selectivity and recruit partner protein molecules to form a pore complex inserted into the membrane [2][5][2,5].
Despite the limited scientific knowledge about the function of aegerolysins, several potential applications are already emerging. Most commonly, some fungal aegerolysins 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][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 aegerolysins 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][3,4]. In addition, antibodies produced against aegerolysins can serve as immuno-diagnostic tools [4]. Due to their variable sequence, aegerolysins 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 aegerolysin genes can promote the secretion of heterologous proteins from fungi in concomitant multi-gene expression [4]. Certain aegerolysins that combine with larger protein partners to form pore-forming complexes can be used to selectively eliminate insect pests [4][10][4,10] or to treat certain types of cancer cells [4][10][4,10].

2. Aegerolysins

ResWearchers have collected (experimental) published data on 23 different aegerolysins and their variants. In total, they were characterized from 18 different species belonging to different kingdoms of tree of life. Twelve of these aegerolysins belong to fungi, four to bacteria, and one to insects and viruses. In fungi, they were characterized from four mushrooms (Agaricomycotina) from the order AgaricalesPleurotus ostreatusP. eryngiiAgrocybe aegerita, and Moniliophthora pernicious, as well as in the ordo PolyporalesLignosus rhinocerotis (Table 1). The origin of these aegerolysins were also four filamentous Eurotimycetes from the ordo EurotialesAspergillus fumigatusA. nigerA. terreus, and A. oryzae (Table 1). Two species belonged to the Sordariomycetes, ordo HypocrealesBeauveria bassiana, and Trichoderma atroviride, and another to the Dothideomycetes, ordo PleosporalesAlternaria geisen (Table 1). There were four bacterial species, two belonging to FirmicutesBacillus thuringiensis and Clostridium bifermentans, and another two to ProteobacteriaPseudomonas aeruginosa and Alcaligenes faecalis (Table 1). Another species belongs to Insecta—LepidopteraNoctuidaePseudoplusia includes, and another to VaridnaviriaAscoviridaeTrichoplusia ni ascovirus 2c (Table 1).
Table 1.
 Organisms that contain aegerolysins according to taxonomy and lifestyles.
Organism Name Other Names Taxonomy Lifestyle/Niche Reference
    Fungi    
Pleurotus ostreatus Oyster mushroom

Hiratake
Agaricomycotina

Agaricales Saprotroph

White rot

Nematocidal
[12][15]
60]. Similar cytolytic effects were observed when PlyB was combined with other Pleurotus-derived aegerolysins, e.g., OlyA6PlyA2 and EryA [53][78]. These heteromeric aegerolysin-based cytolytic complexes have been exploited as potent biopesticides for specific pests, with Cry16Aa/Cry17Aa/Cbm17.1/Cbm17.2 acting against Aedes mosquitoes, and Cry34Ab1/Cry35Ab1, AflP-1A/AflP-1B, OlyA6/PlyBPlyA/PlyB, PlyA2/PlyB, or EryA/PlyB acting against Coleoptera species, especially the western corn rootworm.
Unexpectedly, partner proteins can be classified into five groups (Table 2Figure 2): (1) PlyB and EryB have a similar MACPF fold; (2) the remaining models, including BlyB, showed a reasonably good superposition; BlyB has been shown to best align the structure of bacterial GNIP1Aa, another MACPF domain-containing protein [54][55][52,121]; (3) the Cry35Ab1 structure and (4) the AfIP-1B model do not superimpose with the PlyB structure or with each other; for AfIP-1B, the MACPF domain was found to be insignificant [54][52]; (5) Cry16Aa and Cry17Aa only superimpose with each other.
Table 2.
 List of published aegerolysins.

3. Aegerolysin Binary Partner Proteins

Binary and quaternary cytolytic complexes of bacterial origin in which aegerolysin-like proteins are combined with larger, non-aegerolysin-like protein partner(s), described to date, include: Cry16Aa/Cry17Aa/Cbm17.1/Cbm17.2 from C. bifermentas subsp. malaysia [37][40]Cry34Ab1/Cry35Ab1 from B. thuringiensis [49][50][130,134]; and AflP-1A/AflP-1B from A. faecalis [51][143]. In fungus P. ostreatusPlyA forms a pore embedded in the membrane together with PlyB [52](Figure 1) [
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