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首页> 外文期刊>Biochimica et biophysica acta: BBA: International journal of biochemistry, biophysics and molecular biololgy. Proteins and Proteomics >Cytotoxic ribosome-inactivating lectins from plants
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Cytotoxic ribosome-inactivating lectins from plants

机译：植物的细胞毒性核糖体失活凝集素

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摘要

A class of heterodimeric plant proteins consisting of a carbohydrate-binding B-chain and an enzymatic A-chain which act on ribosomes to inhibit protein synthesis are amongst the most toxic substances known. The best known example of such a toxic lectin is ricin, produced by the seeds of the castor oil plant, Ricinnus communis. For ricin to reach its substrate in the cytosol, it must be endocytosed, transported through the endomembrane system to reach the compartment from which it is translocated into the cytosol, and there avoid degradation making it possible for a few molecules to inactivate a large proportion of the ribosomes and hence kill the cell. Cell entry by ricin involves the following steps: (i) binding to cell-surface glycolipids and glycoproteins bearing beta-1,4-linked galactose residues through the lectin activity of the B-chain (RTB); (ii) uptake by endocytosis and entry into early endosomes, (iii) transfer by vesicular transport to the trans-Golgi network; (iv) retrograde vesicular transport through the Golgi complex and into the endoplasmic reticulum (ER); (v) reduction of the disulfide bond connecting the A- and B-chains: (vi) a partial unfolding of the A-chain (RTA) to enable it to translocate across the ER membrane via the Sec61p translocon using the pathway normally followed by misfolded ER proteins for targeting to the ER-associated degradation (ERAD) machinery; (vi) refolding in the cytosol into a protease-resistant, enzymatically active structure; (vii) interaction with the sarcin-ricin domain (SRD) of the large ribosome subunit RNA followed by cleavage of a single N-glycosidic bond in the RNA to generate a depurinated, inactive ribosome. In addition to the highly specific action on ribosomes, ricin and related ribosome-inactivating proteins (RIPs) have a less specific action in vitro on DNA and RNA substrates releasing multiple adenine, and in some instances, guanine residues. This polynucleotide: adeno sine glycosidase activity has been implicated in the general antiviral, and specifically, the anti HIV-1 activity of several single-chain RIPs which are homologous to the A-chains of the heterodimeric lectins. However, in the absence of clear cause and effect evidence in vivo, such claims should be regarded with caution. (C) 2004 Elsevier B.V. All rights reserved.
机译：一类由碳水化合物结合的B链和酶促的A链组成的异二聚体植物蛋白，其作用于核糖体以抑制蛋白质的合成，是已知的最具毒性的物质。这种有毒的凝集素最著名的例子是蓖麻毒素，由蓖麻油植物蓖麻（Ricinnus communis）的种子产生。为了使蓖麻毒蛋白到达胞质溶胶中的底物，必须对其进行内吞，通过内膜系统运输，使其到达转运至其内的腔室，并避免降解，从而使少数分子失活大部分核糖体，因此杀死细胞。蓖麻毒蛋白进入细胞涉及以下步骤：（i）通过B链（RTB）的凝集素活性与带有β-1,4-连接的半乳​​糖残基的细胞表面糖脂和糖蛋白结合; （ii）通过内吞作用摄取并进入早期内体，（iii）通过囊泡转运转移到反高尔基体网络; （iv）通过高尔基复合体逆行囊泡运输进入内质网（ER）; （v）还原连接A链和B链的二硫键：（vi）A链（RTA）的部分解链，使其能够通过Sec61p translocon使用通常遵循的途径在ER膜上移位错误折叠的ER蛋白用于靶向与ER相关的降解（ERAD）机器; （vi）在胞质溶胶中重折叠成耐蛋白酶的酶活性结构; （vii）与大核糖体亚基RNA的sarcin-ricin域（SRD）相互作用，然后切割RNA中的单个N-糖苷键以生成去嘌呤的，无活性的核糖体。除了对核糖体具有高度特异性的作用外，蓖麻毒素和相关的核糖体失活蛋白（RIP）在体外对释放多个腺嘌呤，在某些情况下还含有鸟嘌呤残基的DNA和RNA底物具有较小的特异性作用。该多核苷酸：腺苷糖苷酶活性已经牵涉到一般的抗病毒剂中，特别是与异二聚凝集素的A链同源的几种单链RIP的抗HIV-1活性。但是，在缺乏体内明确的因果关系证据的情况下，应谨慎考虑此类主张。 （C）2004 Elsevier B.V.保留所有权利。

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