Department of Biochemistry and Molecular Biology, The University of Massachusetts Amherst, Amherst, MA 01003, USA.
Viruses. 2022 Jul 27;14(8):1635. doi: 10.3390/v14081635.
The formation of amyloid fibers is associated with a diverse range of disease and phenotypic states. These amyloid fibers often assemble into multi-protofibril, high-order architectures in vivo and in vitro. Prion propagation in yeast, an amyloid-based process, represents an attractive model to explore the link between these aggregation states and the biological consequences of amyloid dynamics. Here, we integrate the current state of knowledge, highlight opportunities for further insight, and draw parallels to more complex systems in vitro. Evidence suggests that high-order fibril architectures are present ex vivo from disease relevant environments and under permissive conditions in vivo in yeast, including but not limited to those leading to prion formation or instability. The biological significance of these latter amyloid architectures or how they may be regulated is, however, complicated by inconsistent experimental conditions and analytical methods, although the Hsp70 chaperone Ssa1/2 is likely involved. Transition between assembly states could form a mechanistic basis to explain some confounding observations surrounding prion regulation but is limited by a lack of unified methodology to biophysically compare these assembly states. Future exciting experimental entryways may offer opportunities for further insight.
淀粉样纤维的形成与多种疾病和表型状态有关。这些淀粉样纤维通常在体内和体外组装成多原纤维、高阶结构。基于朊病毒的酵母中的朊病毒传播是探索这些聚集态与淀粉样动力学的生物学后果之间联系的一个有吸引力的模型。在这里，我们整合了当前的知识状态，强调了进一步深入了解的机会，并与体外更复杂的系统进行了类比。有证据表明，在与疾病相关的环境中以及在酵母体内允许的条件下，存在高阶纤维结构，包括但不限于导致朊病毒形成或不稳定性的条件。然而，这些后一种淀粉样结构的生物学意义，或者它们如何被调控，由于实验条件和分析方法不一致而变得复杂，尽管 Hsp70 伴侣 Ssa1/2 可能参与其中。组装状态之间的转变可能构成解释朊病毒调控的一些令人困惑的观察结果的机制基础，但由于缺乏统一的生物物理方法来比较这些组装状态，因此受到限制。未来令人兴奋的实验途径可能会提供进一步深入了解的机会。
