Clavin, a Type‐1 Ribosome‐Inactivating Protein from <i>Aspergillus clavatus</i> IF0 8605

Parente, D.; Raucci, Giuseppe; Celano, Bruna; Pacilli, A.; Zanoni, Lorenzo; Canevari, Silvana; Adobati, Elena; Colnaghi, Maria I.; Dosio, Franco; Berlier, Gloria; Cattel, Luigi; Mele, Antonio; Santis, Rita De

doi:10.1111/j.1432-1033.1996.0272u.x

Cited by 31 publications

(13 citation statements)

References 38 publications

(28 reference statements)

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“…α‐Sarcin, restrictocin and Aspf1 are the most exhaustively characterized ribotoxins (Arruda et al , 1992; Gasset et al , 1994; Wool, 1997; Kao et al , 2001; Martínez‐Ruiz et al , 2001; García‐Ortega et al , 2005), but many others have been identified and partially characterized in different fungal species (Lin et al , 1995; Parente et al , 1996; Huang et al , 1997; Wirth et al , 1997; Martínez‐Ruiz et al , 1999a, b). These studies have suggested a high degree of conservation among ribotoxins, as those characterized display amino acid sequence similarities above 85% (Fig.…”

Section: Introductionmentioning

confidence: 99%

Fungal ribotoxins: molecular dissection of a family of natural killers

et al. 2007

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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.

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Section: Introductionmentioning

confidence: 99%

Fungal ribotoxins: molecular dissection of a family of natural killers

et al. 2007

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“…Research on this fungus is sparse compared to other Aspergilli, and the contributions based on nucleotide sequence are limited to the cloning of clavin by Parente et al (1996). Wortman et al (2006) have anticipated that comparative genomics of A. fumigatus, A. clavatus, and N. fischeri will allow the identification of factors responsible for pathogenicity in A. fumigatus.…”

Section: Aspergillus Clavatus Genomicsmentioning

confidence: 98%

Current status of systems biology in Aspergilli

Andersen

Nielsen

2009

Fungal Genetics and Biology

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“…This feature is the explanation of why these proteins display a remarkable but not highly specific antitumoral activity (Jennings et al 1965;Lacadena et al 2007;Olmo et al 2001;Olson and Goerner 1965;Turnay et al 1993). α-Sarcin is the most extensively characterized ribotoxin (Lacadena et al 2007), but many others have been identified and/or characterized in different fungal species (Huang et al 1997;Lin et al 1995;Martínez-Ruiz et al 1999a; Martínez-Ruiz et al 1999b;Parente et al 1996;Varga and Samson 2008;Wirth et al 1997). Most of them show a high degree of conservation with sequence identities above 60% and even higher than 85% in many instances.…”

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Involvement of loop 5 lysine residues and the N-terminal β-hairpin of the ribotoxin hirsutellin A on its insecticidal activity

Olombrada

Garcı́a-Ortega

Lacadena

et al. 2016

Biological Chemistry

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represented by RNase T1. They share a high degree of sequence identity and a common structural fold, including the geometric arrangement of their active sites. However, ribotoxins are larger, with a well-defined N-terminal β-hairpin, and display longer and positively charged unstructured loops. These structural differences account for their cytotoxic properties. Unexpectedly, the discovery of hirsutellin A (HtA), a ribotoxin produced by the invertebrate pathogen Hirsutella thompsonii, showed how it was possible to accommodate these features into a shorter amino acid sequence. Examination of HtA Nterminal β-hairpin reveals differences in terms of length, charge, and spatial distribution.Consequently, four different HtA mutants were prepared and characterized. One of them was the result of deleting this hairpin [∆(8-15)] while the other three affected single Lys residues in its close spatial proximity (K115E, K118E, and K123E). The results obtained support the general conclusion that HtA active site would show a high degree of plasticity, being able to accommodate electrostatic and structural changes not suitable for the other previously known larger ribotoxins, as the variants described here only presented small differences in terms of ribonucleolytic activity and cytotoxicity against cultured insect cells. Keywords:Ribotoxins, hirsutellin A, Ribonucleases, rRNA, insecticidal. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 IntroductionRibotoxins are cytotoxic members of the family of fungal extracellular ribonucleases (RNases) best represented by RNase T1 (Yoshida 2001). They have been shown to be extremely toxic because they exert their ribonucleolytic activity just on a unique phosphodiester bond of the larger molecule of rRNA in the ribosome, leading to protein synthesis inhibition and cell death (Lacadena et al. 2007). This rRNA bond is unique because it is located at an evolutionarily conserved site, the sarcin-ricin loop (SRL), with essential roles in ribosome function (García-Ortega et al. 2010) and maturation (Lo et al. 2010), and it is also the target of the family of plant ribosome-inactivating proteins (RIPs), a group of glycosidases best represented by ricin (Nielsen and Boston 2001).In addition to their ribonucleolytic activity, fungal ribotoxins have the ability to cross lipid membranes in the absence of any known protein receptor, mainly due to their ability to interact with acid phospholipids Martínez-Ruiz et al. 2001;Oñaderra et al. 1993). This feature is the explanation of why these proteins display a remarkable but not highly specific antitumoral activity (Jennings et al. 1965;Lacadena et al. 2007;Olmo et al. 2001;Olson and Goerner 1965;Turnay et al. 1993).α-Sarcin is the most extensively characterized ribotoxin (Lacadena et al. 2007), but many others have been identified and/or characterized in different fungal spec...

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Clavin, a Type‐1 Ribosome‐Inactivating Protein from Aspergillus clavatus IF0 8605

Cited by 31 publications

References 38 publications

Fungal ribotoxins: molecular dissection of a family of natural killers

Fungal ribotoxins: molecular dissection of a family of natural killers

Current status of systems biology in Aspergilli

Involvement of loop 5 lysine residues and the N-terminal β-hairpin of the ribotoxin hirsutellin A on its insecticidal activity

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