RNA N-glycosidase activity of ricin A-chain. Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes.

Endo, Yaeta; Tsurugi, Kunio

doi:10.1016/s0021-9258(18)47538-2

Cited by 885 publications

(94 citation statements)

References 12 publications

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“…Mucoricin has structural and functional similarities to ricin, a prototypic Type 2 RIP consisting of two polypeptide chains (A and B) that are linked by a disulfide bond 24 . The Achain of ricin is an N-glycosidase that is responsible for inactivating ribosomes, and the B chain is a galactose-specific lectin 29 that enables the toxin to bind to target cells 28 .…”

Section: Discussionmentioning

confidence: 99%

“…As reported in Supplementary Table 1, many of the toxin orthologues found in other organisms are annotated as ricin domain-containing proteins or ricin B chain-like lectins. Further detailed bioinformatic analysis of the R. delemar toxin sequence showed a two domain structure similar to that of ricin (Sequence ID: NP_001310630.1) 24 (Fig. 3a).…”

Section: The Hyphae-associated Toxin Has Structural Features Of Ricinmentioning

confidence: 96%

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Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis

Soliman

Baldin

et al. 2021

Nat Microbiol

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Fungi of the order Mucorales cause mucormycosis, a lethal infection with an incompletely understood pathogenesis. We now demonstrate that Mucorales fungi produce a toxin that plays a central role in virulence. Polyclonal antibodies against this toxin inhibit its ability to damage human cells in vitro, and prevent hypovolemic shock, organ necrosis, and death in mice with mucormycosis. RNAi inhibition of the toxin in Rhizopus delemar, compromises the ability of the fungus to damage host cells and attenuates virulence in mice. This 17 kDa toxin has structural and functional features of the plant toxin, ricin, including the ability to inhibit protein synthesis by its N-glycosylase activity, the existence of a motif that mediates vascular leak, and a lectin sequence. Antibodies against the toxin inhibit R. delemar-or toxin-mediated vascular permeability in vitro and cross-react with ricin. A monoclonal anti-ricin B chain antibody binds to the toxin and also inhibits its ability to cause vascular permeability. Therefore, we propose the name "mucoricin" for this toxin. Not only is mucoricin important in the pathogenesis of mucormycosis but our data suggest that a ricinlike toxin is produced by organisms beyond the plant and bacterial kingdoms. Importantly, mucoricin should be a promising therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: The Hyphae-associated Toxin Has Structural Features Of Ricinmentioning

confidence: 96%

Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis

Soliman

Baldin

et al. 2021

Nat Microbiol

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“…Pokeweed antiviral protein (PAP) is a 29 kDa ribosomeinactivating protein (RIP) isolated from the leaves of the pokeweed plant (Phytolacca americana). PAP and other RIPs such as ricin, Shiga toxin from Shigella disentaria and Shiga-like toxin from Escherichia coli catalytically remove an adenine (A4324) residue from the highly conserved sarcin/ ricin loop (S/R) of the large rRNA (1)(2)(3)(4)(5). PAP can also remove an additional adenine and a guanine from the S/R loop (6).…”

Section: Introductionmentioning

confidence: 99%

Generation of pokeweed antiviral protein mutations in Saccharomyces cerevisiae: evidence that ribosome depurination is not sufficient for cytotoxicity

Hudak¹

2004

Nucleic Acids Research

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Pokeweed antiviral protein (PAP) is a ribosome-inactivating protein that depurinates the highly conserved alpha-sarcin/ricin loop in the large rRNA. Here, using site-directed mutagenesis and systematic deletion analysis from the 5' and the 3' ends of the PAP cDNA, we identified the amino acids important for ribosome depurination and cytotoxicity of PAP. Truncating the first 16 amino acids of PAP eliminated its cytotoxicity and the ability to depurinate ribosomes. Ribosome depurination gradually decreased upon the sequential deletion of C-terminal amino acids and was abolished when a stop codon was introduced at Glu-244. Cytotoxicity of the C-terminal deletion mutants was lost before their ability to depurinate ribosomes. Mutations in Tyr-123 at the active site affected cytotoxicity without altering the ribosome depurination ability. Total translation was not inhibited in yeast expressing the non-toxic Tyr-123 mutants, although ribosomes were depurinated. These mutants depurinated ribosomes only during their translation and could not depurinate ribosomes in trans in a translation-independent manner. A mutation in Leu-71 in the central domain affected cytotoxicity without altering the ability to depurinate ribosomes in trans and inhibit translation. These results demonstrate that the ability to depurinate ribosomes in trans in a catalytic manner is required for the inhibition of translation, but is not sufficient for cytotoxicity.

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“…Ricin CS , a mutated Ricin A chain, inactivates eukaryotic ribosomes by hydrolytically cleaving the N-glycosidic bond (A4324) of the 28S ribosomal RNA subunit at high temperatures (30°C), but not at low temperatures (18°C) (Endo et al, 1987; Endo and Tsurugi, 1987; Moffat et al, 1992; Allen et al, 2002). We previously validated the spatiotemporal effect of Ricin CS inhibition in the Drosophila brain using lateral clock neurons.…”

Section: Methodsmentioning

confidence: 99%

CREB repressor in mushroom body enhances Drosophila LTM formation

Chen

Feng

et al. 2021

Preprint

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Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information, however, becomes permanent memory. How the brain gates relevant information into LTM remains unclear. In Drosophila adults, a single training session in an olfactory aversive task is not sufficient to induce protein synthesis-dependent LTM. Instead, multiple spaced training sessions are required. Here, we report that initial learning induces neural activity in the early α/β subset of Kenyon cells of the mushroom body (MB), and output from these neurons inhibits LTM formation. Specifically in response to spaced training, Schnurri activates CREBB expression which then appears to suppress the inhibitory output from MB. One training session can enhance LTM formation when this inhibitory effect is relieved. We propose that learning-induced protein synthesis and spaced training-induced CREBB act antagonistically to modulate output from early α/β MB neurons during LTM formation.

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RNA N-glycosidase activity of ricin A-chain. Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes.

Cited by 885 publications

References 12 publications

Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis

Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis

Generation of pokeweed antiviral protein mutations in Saccharomyces cerevisiae: evidence that ribosome depurination is not sufficient for cytotoxicity

CREB repressor in mushroom body enhances Drosophila LTM formation

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