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 aegerolysins. 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.

New Insights into Interactions between Mushroom Aegerolysins and Membrane Lipids

“…Since VerA aggregated after isolation and had an additional N-terminal sequence which is not characteristic for other aegerolysins, we constructed its truncated form, Δ37VerA, which was not prone to aggregation. Δ37VerA differs from all of the other aegerolysins studied so far [ 1 ] in having a basic rather than acidic isoelectric point. Further, the isolation of MucA was not successful, probably because of the shorter protein sequence resulting in impaired β-sheets.…”

“…The aegerolysin protein family (Pfam 06355) consists of proteins that share some common features: similar low molecular weights (15–20 kDa), low isoelectric points, and β-sandwich structures [ 1 ]. Although they can be found in all domains of life, they are especially widespread in fungi [ 1 ]. The majority of the so far sequenced fungi do not code for aegerolysins, indicating they are not essential proteins [ 1 ].…”

“…Although they can be found in all domains of life, they are especially widespread in fungi [ 1 ]. The majority of the so far sequenced fungi do not code for aegerolysins, indicating they are not essential proteins [ 1 ]. Most of the knowledge about aegerolysins derives from their representatives from the fungal genus Pleurotus .…”

“…Most of the knowledge about aegerolysins derives from their representatives from the fungal genus Pleurotus . Pleurotolysin A (PlyA), ostreolysin A (OlyA), and ostreolysin A6 (OlyA6) from P. ostreatus and pleurotolysin A2 (PlyA2) and erylysin A (EryA) from P. eryngii are the most studied aegerolysins which share another common feature, a lipid-binding ability [ 1 ]. Early experimental data showed that Pleurotus aegerolysins bind to membrane lipid domains composed of sphingomyelin (SM) and cholesterol (Chol) that are characteristic for vertebrates [ 2 , 3 ].…”

A single point mutation expands the applicability of ostreolysin A6 in biomedicine

“…Ostreolysin A6 (OlyA6; UniProt: P83467.2, GeneBank: AGH25589.1; PDB: 6MYI) is a 15-kDa protein produced by the edible mushroom Pleurotus ostreatus (oyster mushroom). It belongs to the larger protein family of aegerolysins (Pfam 06355; InterPro IPR009413), and has recently gained significant interest due to its ability to bind organism-specific membrane sphingolipids 1 – 6 . In addition, in the presence of the 59-kDa protein partner pleurotolysin B (PlyB), which bears a membrane-attack complex/perforin (MACPF) domain and is also produced by P. ostreatus , both OlyA6 and PlyB can assemble into larger pore-forming complexes in target membranes that contain the aegerolysin lipid receptor 1 , 4 , 7 , 8 .…”