Pleurotolysin
TC# 1.C.97.1.1
, a

sphingomyelin Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a ethano ...

-specific

cytolysin Cytolysin refers to the substance secreted by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are n ...

. Its A (17 kDa
Q8X1M9
and B (59 kDa
Q5W9E8
components are assembled into a transmembrane pore complex. The Pleurotolysin Pore-Forming (Pleurotolysin) Family
TC# 1.C.97
is a family of pore forming proteins belonging to the MACPF superfamily.

Function

Proteins with membrane-attack complex/perforin (MACPF) domains have a variety of biological roles, including defense and attack, organismal development, and cell adhesion and signaling. The distribution of these proteins in fungi appears to be restricted to some

Pezizomycotina Pezizomycotina make up most of the Ascomycota fungi and include most lichenized fungi too. Pezizomycotina contains the filamentous ascomycetes and is a subdivision of the Ascomycota (fungi that form their spores in a sac-like ''ascus''). It is mo ...

and

Basidiomycota Basidiomycota () is one of two large divisions that, together with the Ascomycota, constitute the subkingdom Dikarya (often referred to as the "higher fungi") within the kingdom Fungi. Members are known as basidiomycetes. More specifically, Basi ...

species only, in correlation with the aegerolysins
PF06355
. These two protein groups coincide in only a few species, and they operate as cytolytic bi-component pore-forming agents. Representative proteins include pleurotolysin B, which has a

MACPF The Membrane Attack Complex/Perforin (MACPF) superfamily, sometimes referred to as the MACPF/CDC superfamily, is named after a domain that is common to the membrane attack complex (MAC) proteins of the complement system (C6, C7, C8α, C8β and ...

domain, the aegerolysin-like protein pleurotolysin A, and the very similar ostreolysin A
TC# 1.C.97.3.2
that has been purified from oyster mushroom (''

Pleurotus ostreatus ''Pleurotus ostreatus'', the oyster mushroom, oyster fungus, or hiratake, is a common edible mushroom. It was first cultivated in Germany as a subsistence measure during World War I and is now grown commercially around the world for food. It is ...

''). These act in concert to perforate natural and artificial lipid membranes with high cholesterol and sphingomyelin contents. The complex has a 13-meric rosette-like structure with a central lumen that is ~ 4-5 nm in diameter. The opened transmembrane pore is non-selectively permeable to ions and smaller neutral solutes, and is a cause of cytolysis of a colloid-osmotic type.

Research

Sakurai et al. 2004 cloned complementary and genomic DNAs encoding pleurotolysin, and studied pore-forming properties of recombinant proteins. Recombinant pleurotolysin A lacking the first

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

was purified as a 17-kDa protein with

-binding activity. The cDNA for pleurotolysin B encoded a precursor consisting of 523 amino acyl residues, of which 48 N-terminal amino acyl residues were absent in natural pleurotolysin B. Mature and precursor forms of pleurotolysin B were expressed as insoluble 59- and 63-kDa proteins, respectively. Although neither recombinant pleurotolysin A nor B alone was hemolytically active at higher concentrations of up to 100 mg/ml, they cooperatively assembled into a membrane pore complex on human erythrocytes and lysed the cell.

Homologues

In this TC family, both constituents of pleurotolysin and ostreolysin (A and B) are included unde
TC#s 1.C.97.1.1
an
1.C.97.1.2
respectively. However, homologues of Pleurotolysin B are found unde
TC#s 1.C.97.1.3

1.C.97.1.9
while homologues of Pleurotolysin A are found unde
TC#s 1.C.97.2.1

1.C.97.2.4
an
TC#s 1.C.97.3.1

1.C.97.3.8
Pleurotolysins A are not homologous to Pleurotolysins B. While some homologues depend on the presence of both constituents for pore formation, as noted for both pleurotolysin and ostreolysin, some homologues of both A and B can form pores without the other. While Pleurotolysin B is in the MACPF superfamily (TC# 1.C.39) while Pleurotolysin A is in the Aegerolysin superfamily.

Erylysin

Another two-component hemolysin, erylysin A and B (EryA and EryB
TC# 1.C.97.1.2
, was isolated from an edible mushroom, ''Pleurotus eryngii''. Hemolytic activity was exhibited only by the EryA and EryB mixture.

Aegerolysin

While Pleurotolysin B is in the MACPF superfamily
TC# 1.C.39
, Pleurotolysin A is in the Aegerolysin superfamily. Several members of the Aegerolysin family have been used as tools to detect and visualize ceramide phosphoethanolamine, a major sphingolipid in invertebrates but not in animals. It may be distantly related to members of the Equinatoxin Family
TC# 1.C.38
. The aegerolysin family consists of several bacterial and eukaryotic aegerolysin-like proteins. It has been found that aegerolysin and ostreolysin are expressed during formation of primordia and fruiting bodies and possibly play a role in the initial phase of fungal fruiting. The bacterial members of this family are expressed during sporulation. Ostreolysin is cytolytic to various erythrocytes and tumor cells because of pore formation. Several members of the Aegerolysin family have been used as tools to detect and visualize ceramide phosphoethanolamine, a major sphingolipid in invertebrates but not in animals. It may be distantly related to members of the Equinatoxin Family
TC# 1.C.38
.

References

{{Dual, source=Transporter Classification Database, sourcepath=http://www.tcdb.org/search/result.php?tc=1.C.97, sourcearticle=1.C.97 The Pleurotolysin Pore-Forming (Pleurotolysin) Family, date=20:02, 16 February 2016 (UTC) Protein families Transmembrane transporters