Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Microb Cell Fact. 2012 Jun 25;11:89. doi: 10.1186/1475-2859-11-89.
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.
朊病毒最初被鉴定为与哺乳动物致命性脑部疾病相关的传染性蛋白。然而，真菌朊病毒表现为表观遗传调控因子，可以改变一系列细胞过程。这些蛋白质作为自我维持的淀粉样聚集物进行传播，是结构遗传的一个例子。研究最充分的例子是 Sup35 和 Ure2 酵母蛋白，分别对应于[PSI+]和[URE3]表型。
在这里，我们表明 Sup35 的朊病毒结构域（Sup35-NM）和 Ure2 蛋白（Ure2p）在细菌中表达时都会形成包含体（IBs），表现出类似淀粉样的特性。这些细胞内聚集体模板构象变化并促进同源但非异源的可溶性朊病毒分子的聚集。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，表明这些沉积物中至少有一部分蛋白采用了传染性朊病毒折叠。
朊病毒遗传的一个重要特征是存在菌株，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，表现出强和弱[PSI+]表型的受感染酵母细胞的比例取决于在大肠杆菌中形成朊病毒原纤维的条件，这表明细菌系统可能成为产生朊病毒菌株多样性的有用工具。
