Amatoxins, Phallotoxins, Phallolysin, and Antamanide: The Biologically Active Components of PoisonousAmanitaMushroom

Abstract

This review gives a comprehensive account of the molecular toxicology of the bicyclic peptides obtained from the poisonous mushrooms of the genus Amanita. The discussion of the biochemical events will be preceded by a consideration of the chemistry of the toxic peptides. The structural features essential for biological activities of both the amatoxins and the phallotoxins will be discussed, also including the most important analytical data. Similar consideration will be given to antamanide, a cyclic peptide, which counteracts phalloidin. In addition, the phallolysins, three cytolytic proteins from Amanita phalloides will be discussed. The report on the biological activity of the amatoxins will deal with the sensitivity of the different RNA-polymerases towards the toxins and with their action on various cell types. Consideration will also be given to systems in which alpha-amanitin was used and can be used as a molecular tool; in the past, many investigators used the inhibitor in molecular biology, genetics, and even in physiological research. As for the phallotoxins, discussion of the affinity of these toxins for actin is provied. Further discussion attempts to understand the course of intoxication by filling in the gap between the first molecular event, formation of microfilaments, and the various lesions in hepatocytes during the intoxication.

Mutational analysis of arginine 177 in the nucleotide binding site of beta-actin

“…Phalloidin binds to filamentous actin, in a 1 : 1 stoichiometry with respect to actin monomers, and lowers the A cc [36,37], resulting in an apparent stabilization of the filaments. It is shown here that the R177D mutation caused a large increase in A cc , and that phalloidin binding decreased A cc twofold to threefold, although not to the low levels reached with wildtype actin.…”

Microinjection of actin-binding proteins and actin antibodies demonstrates involvement of nuclear actin in transcription of lampbrush chromosomes

“…In order to examine possible effects of induced polymerization of nuclear actin on transcription, we microinjected phalloidin (1 mg/ml), a mushroom drug known to stabilize and arrest the polymer form of actin (Wieland and Faulstich, 1978), into nuclei of living oocytes. This resulted in the instantaneous "hardening" of the whole nuclear content (not shown).…”

Cyclopeptides from Amanita exitialis

“…2 Interestingly, a cyclic decapeptide, antamanide, acting as a potential anti-toxin against the effects of phallotoxins and amatoxins has been also isolated from an Amanita mushroom, the death cap A. phalloides. 3,4 Amanita exitialis, endemic to Guangzhou, Guangdong Province, China, is a new Amanita species originally described in 2001. 5 This mushroom annually comes out at the beginning of March and disappears at the end of April in the north suburbs of Guangzhou.…”