Molecular Pathology of the Amanita Peptides

Abstract

For both families of the toxic peptides of Amanita mushrooms, the phallotoxins as well as the amatoxins, the targets which are mainly involved in the pathological processes, have been identified. In both cases, by specific binding of the relatively small, cyclic peptides, conformational changes are established in high molecular proteins, thus disturbing their normal functions in the cells. The amatoxins are directed to enzymes in the nucleus, which are responsible for the synthesis of RNAs, chiefly heterodisperse nuclear (hn)RNAs, the precursors of messenger (m)RNAs, thus causing a very effective inhibition of transcription and, consequently, of protein synthesis. The phallotoxins bind very strongly to filamentous actin (F-actin), thus stabilizing the high polymer filamentous structure and disturbing the congruous polymer-monomer state of this cytoskeletal protein. The liver is the organ almost exclusively affected by both classes; in amatoxin poisoning, the kidneys are also affected.