Cardiology Research Center, Moscow, Russia.
Prion. 2010 Jan-Mar;4(1):45-52. doi: 10.4161/pri.4.1.11074. Epub 2010 Jan 18.
In eukaryotic cells amyloid aggregates may incorporate various functionally unrelated proteins. In mammalian diseases this may cause amyloid toxicity, while in yeast this could contribute to prion phenotypes. Insolubility of amyloids in the presence of strong ionic detergents, such as SDS or sarcosyl, allows discrimination between amorphous and amyloid aggregates. Here, we used this property of amyloids to study the interdependence of their formation in yeast. We observed that SDS-resistant polymers of proteins with extended polyglutamine domains caused the appearance of SDS or sarcosyl-insoluble polymers of three tested chromosomally-encoded Q/N-rich proteins, Sup35, Rnq1 and Pub1. These polymers were non-heritable, since they could not propagate in the absence of polyglutamine polymers. Sup35 prion polymers caused the appearance of non-heritable sarcosyl-resistant polymers of Pub1. Since eukaryotic genomes encode hundreds of proteins with long Q/N-rich regions, polymer interdependence suggests that conversion of a single protein into polymer form may significantly affect cell physiology by causing partial transfer of other Q/N-rich proteins into a non-functional polymer state.
在真核细胞中，淀粉样纤维可能会结合各种功能上不相关的蛋白质。在哺乳动物疾病中，这可能导致淀粉样毒性，而在酵母中，这可能导致朊病毒表型。在存在强离子去污剂（如 SDS 或肌氨酸）的情况下，淀粉样物质不溶，这允许区分无定形和淀粉样纤维聚集物。在这里，我们利用淀粉样纤维的这一特性来研究酵母中它们形成的相互依赖性。我们观察到，具有延伸多谷氨酰胺结构域的蛋白质的 SDS 抗性聚合物导致了三种测试的染色体编码的 Q/N 富含蛋白质（Sup35、Rnq1 和 Pub1）的 SDS 或肌氨酸不溶性聚合物的出现。这些聚合物是不可遗传的，因为它们在没有多谷氨酰胺聚合物的情况下无法传播。Sup35 朊病毒聚合物导致 Pub1 的非遗传肌氨酸抗性聚合物的出现。由于真核基因组编码了数百种具有长 Q/N 富含区域的蛋白质，聚合物的相互依赖性表明，单个蛋白质转化为聚合物形式可能会通过将其他 Q/N 富含蛋白质部分转移到无功能的聚合物状态，从而对细胞生理学产生重大影响。
