Targeting ricin to the ribosome.

Targeting ricin to the ribosome.
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DOI:
10.1016/j.toxicon.2013.02.001
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发表时间:
2013-07
期刊:
影响因子:
2.8
通讯作者:
Tumer, Nilgun E.
Tumer, Nilgun E.
中科院分区:
医学4区
文献类型:
--
作者:
May, Kerrie L.;Yan, Qing;Tumer, Nilgun E.

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蓖麻毒素是一种对哺乳动物细胞有剧毒的植物毒素,引起了生物恐怖主义的关注。蓖麻毒素属于一个功能相关的毒素家族,统称为核糖体失活蛋白(RIPs),它使核糖体失活并停止蛋白质合成。目前还没有针对蓖麻毒素或相关rip的特异性解毒剂。蓖麻毒素的酶亚基是一种n -糖苷酶,它可以在28S rRNA的sarcin/ricin环(SRL)中去嘌呤残基。这种去嘌呤活性抑制翻译及其生物化学已被深入研究。然而,最近的发展描绘了一幅更复杂的毒性图景,核糖体蛋白和细胞信号通路有助于蓖麻毒素的效力。特别是,一些研究已经确立了核糖体柄结构在促进蓖麻毒素和其他rip的去嘌呤活性和核糖体特异性方面的重要性。这篇综述强调了毒素-核糖体相互作用的最新进展,并探讨了这些相互作用对毒性和治疗干预的意义。
The plant toxin ricin is highly toxic for mammalian cells and is of concern for bioterrorism. Ricin belongs to a family of functionally related toxins, collectively referred to as ribosome inactivating proteins (RIPs), which disable ribosomes and halt protein synthesis. Currently there are no specific antidotes against ricin or related RIPs. The enzymatic subunit of ricin is an N-glycosidase that depurinates a universally conserved adenine residue within the sarcin/ricin loop (SRL) of the 28S rRNA. This depurination activity inhibits translation and its biochemistry has been intensively studied. Yet, recent developments paint a more complex picture of toxicity, with ribosomal proteins and cellular signaling pathways contributing to the potency of ricin. In particular, several studies have now established the importance of the ribosomal stalk structure in facilitating the depurination activity and ribosome specificity of ricin and other RIPs. This review highlights recent developments defining toxin-ribosome interactions and examines the significance of these interactions for toxicity and therapeutic intervention.
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影响因子: 4.8
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