title: Fungal ribotoxins: molecular dissection of a family of natural killers.
abstract: RNase T1 is the best known representative of a large family of ribonucleolytic proteins secreted by fungi, mostly Aspergillus and Penicillium species. Ribotoxins stand out among them by their cytotoxic character. They exert their toxic action by first entering the cells and then cleaving a single phosphodiester bond located within a universally conserved sequence of the large rRNA gene, known as the sarcin-ricin loop. This cleavage leads to inhibition of protein biosynthesis, followed by cellular death by apoptosis. Although no protein receptor has been found for ribotoxins, they preferentially kill cells showing altered membrane permeability, such as those that are infected with virus or transformed. Many steps of the cytotoxic process have been elucidated at the molecular level by means of a variety of methodological approaches and the construction and purification of different mutant versions of these ribotoxins. Ribotoxins have been used for the construction of immunotoxins, because of their cytotoxicity. Besides this activity, Aspf1, a ribotoxin produced by Aspergillus fumigatus, has been shown to be one of the major allergens involved in allergic aspergillosis-related pathologies. Protein engineering and peptide synthesis have been used in order to understand the basis of these pathogenic mechanisms as well as to produce hypoallergenic proteins with potential diagnostic and immunotherapeutic applications.
authors.affiliation: Departamento de Bioquímica y Biología Molecular I, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Lacadena
authors.forename: Elisa
authors.initials: E
authors.lastname: Alvarez-García
authors.forename: Nelson
authors.initials: N
authors.lastname: Carreras-Sangrà
authors.forename: Elías
authors.initials: E
authors.lastname: Herrero-Galán
authors.forename: Jorge
authors.initials: J
authors.lastname: Alegre-Cebollada
authors.forename: Lucía
authors.initials: L
authors.lastname: García-Ortega
authors.forename: Mercedes
authors.initials: M
authors.lastname: Oñaderra
authors.forename: José G
authors.initials: JG
authors.lastname: Gavilanes
authors.forename: Alvaro
authors.initials: A
authors.lastname: Martínez del Pozo
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001230:Aspergillus / Q000737:chemistry; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005658:Fungi / Q000737:chemistry*; D000922:Immunotoxins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009183:Mycotoxins / Q000737:chemistry / Q000378:metabolism*; D010407:Penicillium / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry
chemical_list: D000485:Allergens; D005656:Fungal Proteins; D000922:Immunotoxins; D009183:Mycotoxins; C014801:alpha-sarcin; D012313:RNA; D004722:Endoribonucleases; D012260:Ribonucleases