Purification, characterization and cytotoxicity assessment of Ageritin: The first ribotoxin from the basidiomycete mushroom Agrocybe aegerita

Several species belonging to Ascomycota phylum produce extracellular ribonucleases, known as ribotoxins, which exhibit RNase activity through the cleavage of a single phosphodiester bond, located at the universally conserved sarcin/ricin loop of the large rRNA leading to inhibition of protein biosyn...

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Bibliographic Details
Published in:Biochimica et biophysica acta. General subjects Vol. 1861; no. 5; pp. 1113 - 1121
Main Authors: Landi, Nicola, Pacifico, Severina, Ragucci, Sara, Iglesias, Rosario, Piccolella, Simona, Amici, Adolfo, Di Giuseppe, Antonella M.A., Di Maro, Antimo
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.05.2017
Subjects:
Agaricales - chemistry
Ageritin
Agrocybe - chemistry
Agrocybe aegerita
amino acid composition
Amino Acid Sequence
antineoplastic activity
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Ascomycota
Basidiomycota - chemistry
brain
Caspase 8 - metabolism
Caspase 9 - metabolism
caspase-9
Cell Line, Tumor
circular dichroism spectroscopy
Cytotoxicity
Endoribonucleases - metabolism
Fungal Proteins - metabolism
genetically modified organisms
Humans
mushrooms
neoplasms
pest resistance
Protein Biosynthesis - drug effects
protein synthesis
Ribonuclease activity
ribonucleases
Ribonucleases - chemistry
Ribonucleases - pharmacology
ribosomal RNA
Ribosomes - chemistry
Ribosomes - metabolism
Ribotoxins
ricin
Ricin - metabolism
RNA, Ribosomal - metabolism
structure-activity relationships
therapeutics
vinblastine
Ribotoxins
Ribonuclease activity
Cytotoxicity
Ageritin
Agrocybe aegerita
Apoptosis
ISSN:0304-4165, 1872-8006
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Summary:Several species belonging to Ascomycota phylum produce extracellular ribonucleases, known as ribotoxins, which exhibit RNase activity through the cleavage of a single phosphodiester bond, located at the universally conserved sarcin/ricin loop of the large rRNA leading to inhibition of protein biosynthesis. Clarifying the structure-function relationship in ribotoxins is interesting for their use in human tumour therapy and in construction of pest resistant transgenic plants. The ribotoxin Ageritin has been isolated for the first time from the Basidiomycetes class. The enzyme, characterized by means of its amino acid composition, N-terminal sequence and a circular dichroism, structurally differs from Ascomycota ribotoxin prototype, although it was able, as α-sarcin, to release a specific α-fragment. However, it does not display aspecific ribonucleolytic activity. Ageritin exerts cytotoxicity and cell death promoting effects towards CNS model cell lines (SK-N-BE(2)-C, U-251 and C6), as vinblastine, a plant alkaloid used in cancer therapy. Moreover, our results indicate that Ageritin initially activates caspase-8, whereas caspase-9 cleavage was not detected, demonstrating the involvement of an extrinsic apoptotic pathway. Our findings show that Ageritin is the earliest diverging member of the Ascomycota ribotoxin family, suggesting that ribotoxins are more widely distributed among fungi than previously believed. Ageritin, structurally different from the widely known Ascomycota ribotoxins, with promising anti-cancer properties vs. aggressive brain tumours, has been found from the basidiomycete fungus Agrocybe aegerita. Finally, this finding highlights that the ribotoxin family has divergent members in Basidiomycota phylum, whose structural and functional characterization can give new information on ribotoxin or ribonuclease superfamilies. [Display omitted] •Ageritin is a ribotoxin purified from Agrocybe aegerita mushroom.•This enzyme is the first ribotoxin from the Basidiomycetes class.•Ageritin is enzymatically similar to alpha-sarcin, a ribotoxin prototype.•This protein is structurally different from the widely known Ascomycota ribotoxins.•Ageritin inhibits the cell proliferation of several CNS model cell lines via apoptosis.
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ISSN:0304-4165
1872-8006
DOI:10.1016/j.bbagen.2017.02.023