Malinovska Liliana, Alberti Simon
a Max Planck Institute of Molecular Cell Biology and Genetics ; Dresden , Germany.
Prion. 2015;9(5):339-46. doi: 10.1080/19336896.2015.1099799.
Prion-like proteins can undergo conformational rearrangements from an intrinsically disordered to a highly ordered amyloid state. This ability to change conformation is encoded in distinctive domains, termed prion domains (PrDs). Previous work suggests that PrDs change conformation to affect protein function and create phenotypic diversity. More recent work shows that PrDs can also undergo many weak interactions when disordered, allowing them to organize the intracellular space into dynamic compartments. However, mutations within PrDs and altered aggregation properties have also been linked to age-related diseases in humans. Thus, the physiological role of prion-like proteins, the mechanisms regulating their conformational promiscuity and the links to disease are still unclear. Here, we summarize recent work with prion-like proteins in Dictyostelium discoideum. This work was motivated by the finding that D. discoideum has the highest content of prion-like proteins of all organisms investigated to date. Surprisingly, we find that endogenous and exogenous prion-like proteins remain soluble in D. discoideum and do not misfold and aggregate. We provide evidence that this is due to specific adaptations in the protein quality control machinery, which may allow D. discoideum to tolerate its highly aggregation-prone proteome. We predict that D. discoideum will be an important model to study the function of prion-like proteins and their mechanistic links to disease.
朊病毒样蛋白可经历从内在无序状态到高度有序淀粉样状态的构象重排。这种改变构象的能力由独特的结构域编码，称为朊病毒结构域（PrDs）。先前的研究表明，PrDs通过改变构象来影响蛋白质功能并产生表型多样性。最近的研究表明，PrDs在无序状态时也能发生许多弱相互作用，从而使它们能够将细胞内空间组织成动态区室。然而，PrDs内的突变和聚集特性的改变也与人类的年龄相关疾病有关。因此，朊病毒样蛋白的生理作用、调节其构象多态性的机制以及与疾病的联系仍不清楚。在这里，我们总结了近期关于盘基网柄菌中朊病毒样蛋白的研究工作。这项工作的动机是发现盘基网柄菌在迄今为止研究的所有生物中朊病毒样蛋白含量最高。令人惊讶的是，我们发现内源性和外源性朊病毒样蛋白在盘基网柄菌中保持可溶状态，不会错误折叠和聚集。我们提供的证据表明，这是由于蛋白质质量控制机制的特定适应性变化，这可能使盘基网柄菌能够耐受其极易聚集的蛋白质组。我们预测，盘基网柄菌将成为研究朊病毒样蛋白功能及其与疾病的机制联系的重要模型。
