Membrane cholesterol and sphingomyelin, and ostreolysin A are obligatory for pore-formation by a MACPF/CDC-like pore-forming protein, pleurotolysin B

Ota, Katja; Leonardi, Adrijana; Mikelj, Miha; Skočaj, Matej; Wohlschlager, Therese; Künzler, Markus; Aebi, Markus; Narat, Mojca; Križaj, Igor; Anderluh, Gregor; Sepčić, Kristina; Maček, Peter

doi:10.1016/j.biochi.2013.06.012

Cited by 72 publications

(105 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…aegerita and recombinant terrelysin from Aspergillus terreus have been suggested to be hemolytic (Berne et al 2002;Nayak et al 2011a). On the contrary, OlyA, pleurotolysin A (PlyA), and erylysin A (EryA), which are aegerolysins from Pleurotus spp., are not hemolytically active per se, as each functions as part of the bi-component pore-forming proteins that include pleurotolysin B (PlyB) and erylysin B (EryB), respectively, which belong to the family of proteins with a membrane attack complex/ perforin (MACPF) domain Gilbert et al 2013;Ota et al 2013;Shibata et al 2010;Tomita et al 2004). As well as having hemolytic activity, OlyA (or an isoformic PlyA) and its partnering protein (PlyB, with the MACPF domain) can also form pores in lipid vesicles composed of either total erythrocyte lipids or sphingomyelin and cholesterol (Ota et al 2013;Sepčić et al 2004;Tomita et al 2004).…”

Section: Activities Of the Aegerolysin Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

Fungal aegerolysin-like proteins: distribution, activities, and applications

Novak

Kraševec

Skočaj

et al. 2014

Appl Microbiol Biotechnol

Self Cite

View full text Add to dashboard Cite

The aegerolysin protein family (from aegerolysin of the mushroom Agrocybe aegerita) comprises proteins of ∼15-20 kDa from various eukaryotic and bacterial taxa. Aegerolysins are inconsistently distributed among fungal species, and variable numbers of homologs have been reported for species within the same genus. As such noncore proteins, without a member of a protein family in each of the sequenced fungi, they can give insight into different species-specific processes. Some aegerolysins have been reported to be hemolytically active against mammalian erythrocytes. However, some function as bi-component proteins that have membrane activity in concert with another protein that contains a membrane attack complex/perforin domain. The function of most of aegerolysins is unknown, although some have been suggested to have a role in development of the organism. Potential biotechnological applications of aegerolysins are already evident, despite the limited scientific knowledge available at present. Some mushroom aegerolysins, for example, can be used as markers to detect and label specific membrane lipids. Others can be used as biomarkers of fungal exposure, where their genes can serve as targets for detection of fungi and their progression during infectious diseases. Antibodies against aegerolysins can also be raised as immuno-diagnostic tools. Aegerolysins have been shown to serve as a species determination tool for fungal phytopathogen isolates in terms of some closely related species, where commonly used internal transcribed spacer barcoding has failed. Moreover, strong promoters that regulate aegerolysin genes can promote secretion of heterologous proteins from fungi and have been successfully applied in simultaneous multi-gene expression techniques.

show abstract

Section: Activities Of the Aegerolysin Proteinsmentioning

confidence: 99%

“…When native ostreolysin (Oly=OlyA contaminated with minor amounts of PlyB; Ota et al 2013) was applied externally at 1 to 250 ng/mm 2 to solid nutrient media inoculated with mycelia of Pl. ostreatus, slight and transient inhibition of mycelial growth was observed, in comparison with control plates.…”

Section: Activities Of the Aegerolysin Proteinsmentioning

confidence: 99%

Fungal aegerolysin-like proteins: distribution, activities, and applications

Novak

Kraševec

Skočaj

et al. 2014

Appl Microbiol Biotechnol

Self Cite

View full text Add to dashboard Cite

show abstract

“…EqT II recognises the sphingomyelin head group [5], while Oly specifically binds to membrane domains containing both sphingomyelin and cholesterol [2,6]. This binding results in protein oligomerization at the membrane surface, and the formation of transmembrane pores, leading to colloid-osmotic mechanisms resulting in cell lysis.…”

Section: Introductionmentioning

confidence: 99%

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

Frangež¹,

Šuput²,

Molgó³

et al. 2017

Preprint

View full text Add to dashboard Cite

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

show abstract

“…This protein was shown to be highly similar to Aa-Pri1, a predicted protein from Agrocybe aegerita [8] and similar to Asp-haemolysin from Aspergillus fumigatus [9] and the non-haemolytic proteins P16 and P18 from the bacterium Clostridium bifermentans [10]. Recently, Oly was reported to consist of two proteins, ostreolysin A (OlyA) and pleurotolysin B (PlyB) with membrane-attack complex/perforin (MACPF) domain [11], in a respective 9:1 molar ratio and with molecular masses of ∼15 and ∼59 kDa, respectively [2]. These proteins form a 13-meric rosette-like structure which has a central hydrophilic pore of about 4-5 nm diameter.…”

Section: Originmentioning

confidence: 99%

“…Recently, Oly was found to consist of two proteins, ostreolysin A (OlyA) and pleurotolysin B (PlyB) in a 9:1 molar ratio, respectively, and with respective ∼15 and ∼59 kDa molecular masses [2]. Both OlyA/PlyB and EqT II are characterized structurally by a dominant β-structure scaffold that keeps a constant global domain tertiary structure, while the polypeptide elements needed for membrane penetration are provided by minor local conformational changes [3,4].…”

Section: Introductionmentioning

confidence: 99%

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

Frangež¹,

Šuput²,

Molgó³

et al. 2017

Preprint

View full text Add to dashboard Cite

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equine, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin, (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema, (iii) dose-dependent contraction of coronary vessels, (iv) haemolysis with pronounced hyperkalaemia in vivo, (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

show abstract

Membrane cholesterol and sphingomyelin, and ostreolysin A are obligatory for pore-formation by a MACPF/CDC-like pore-forming protein, pleurotolysin B

Cited by 72 publications

References 49 publications

Fungal aegerolysin-like proteins: distribution, activities, and applications

Fungal aegerolysin-like proteins: distribution, activities, and applications

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins

Contact Info

Product

Resources

About