Yeast prions form infectious amyloid inclusion bodies in bacteria.
Yeast prions form infectious amyloid inclusion bodies in bacteria.
复制标题
DOI：
10.1186/1475-2859-11-89
复制
发表时间：
2012-06-25
影响因子：
6.4
通讯作者：
Ventura S
中科院分区：
文献类型：
--
作者：
Espargaró A;Villar-Piqué A;Sabaté R;Ventura S
Prion首先被确定为与哺乳动物致命的脑部疾病有关的感染性蛋白质。然而，真菌蛋白起表观遗传调节剂的作用，可以改变一系列细胞过程。这些蛋白质以自我永续的淀粉样聚集体的形式繁殖，这是结构遗传的一个例子。最典型的例子是Sup35和Ure2酵母蛋白，分别对应于[PSI+]和[URE3]表型。在这里，我们发现Sup35的Prion结构域(Sup35-NM)和Ure2蛋白(Ure2p)都形成了包涵体(IBS)，当在细菌中表达时，显示出淀粉样属性。这些细胞内聚集体以构象变化为模板，促进同源的、但不是异源的可溶原性分子的聚集。此外，在Sup35-NM的情况下，纯化的IBS能够在酵母中诱导不同的[PSI+]表型，这表明至少有一部分嵌入这些沉淀物中的蛋白质采用了具有感染性的Prion折叠。Pron遗传的一个重要特征是存在菌株，这些菌株是由同一多肽的不同构象编码的表型变体。我们在这里表明，感染的酵母细胞显示强和弱[PSI+]表型的比例取决于在大肠杆菌中形成原生聚集体的条件，这表明细菌系统可能成为产生Pron菌株多样性的有用工具。
Prions were first identified as infectious proteins associated with fatal brain diseases in mammals. However, fungal prions behave as epigenetic regulators that can alter a range of cellular processes. These proteins propagate as self-perpetuating amyloid aggregates being an example of structural inheritance. The best-characterized examples are the Sup35 and Ure2 yeast proteins, corresponding to [PSI+] and [URE3] phenotypes, respectively. Here we show that both the prion domain of Sup35 (Sup35-NM) and the Ure2 protein (Ure2p) form inclusion bodies (IBs) displaying amyloid-like properties when expressed in bacteria. These intracellular aggregates template the conformational change and promote the aggregation of homologous, but not heterologous, soluble prionogenic molecules. Moreover, in the case of Sup35-NM, purified IBs are able to induce different [PSI+] phenotypes in yeast, indicating that at least a fraction of the protein embedded in these deposits adopts an infectious prion fold. An important feature of prion inheritance is the existence of strains, which are phenotypic variants encoded by different conformations of the same polypeptide. We show here that the proportion of infected yeast cells displaying strong and weak [PSI+] phenotypes depends on the conditions under which the prionogenic aggregates are formed in E. coli, suggesting that bacterial systems might become useful tools to generate prion strain diversity.
登录
查看更多内容
影响因子：
7.7
作者：
Hess, Simone;Lindquist, Susan L.;Scheibel, Thomas
通讯作者：
Scheibel, Thomas
影响因子：
3.4
作者：
Castillo, Virginia;Espargaro, Alba;Ventura, Salvador
通讯作者：
Ventura, Salvador
影响因子：
46.9
作者：
Bach, S;Talarek, N;Blondel, M
通讯作者：
Blondel, M
影响因子：
3
作者：
Bousset, L;Briki, F;Melki, R
通讯作者：
Melki, R
影响因子：
3.5
作者：
Espargaro, Alba;Sabate, Raimon;Ventura, Salvador
通讯作者：
Ventura, Salvador