Yeast Short-Lived Actin-Associated Protein Forms a Metastable Prion in Response to Thermal Stress.
Yeast Short-Lived Actin-Associated Protein Forms a Metastable Prion in Response to Thermal Stress.
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酵母短寿命肌动蛋白相关的蛋白质响应热应激而形成亚稳态的prion。
DOI：
10.1016/j.celrep.2016.12.082
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发表时间：
2017-01-17
期刊：
影响因子：
8.8
通讯作者：
Wilkinson KD
中科院分区：
文献类型：
--
作者：
Chernova TA;Kiktev DA;Romanyuk AV;Shanks JR;Laur O;Ali M;Ghosh A;Kim D;Yang Z;Mang M;Chernoff YO;Wilkinson KD
自我延续的有序蛋白质聚集体（淀粉样蛋白和朊病毒）与多种神经退行性疾病有关。尽管环境因素与某些淀粉样蛋白疾病有关，但其作用的分子基础仍不清楚。我们采用内源性酵母朊病毒作为模型系统来研究淀粉样蛋白形成的环境控制。一种短寿命的肌动蛋白相关酵母蛋白 Lsb2 可以通过细胞骨架和泛素依赖性过程调节的模式触发其他蛋白形成朊病毒。在这里，我们表明，这种异源朊病毒诱导是由于 Lsb2 能够形成短暂的朊病毒状态，这是响应热应力而产生的。 Lsb2 的朊病毒诱导活性的进化获得可追溯到单个氨基酸的变化，这与酵母谱系中耐热性的获得相一致。这提出了一种有趣的可能性，即瞬时朊病毒的形成可能有助于 Lsb2 在较高温度下发挥作用。朊病毒是可传播的蛋白质聚集体。切尔诺瓦等人。研究表明，酵母短命细胞骨架蛋白 Lsb2 的瞬时朊病毒是由热应激触发的，并诱导其他朊病毒。 Lsb2 的朊病毒诱导活性的进化获得可追溯到单个氨基酸取代，这与酵母适应更高的温度相一致。
Self-perpetuating ordered protein aggregates (amyloids and prions) are associated with a variety of neurodegenerative disorders. Although environmental agents have been linked to certain amyloid diseases, the molecular basis of their action remains unclear. We have employed endogenous yeast prions as a model system to study environmental control of amyloid formation. A short-lived actin-associated yeast protein Lsb2 can trigger prion formation by other proteins in a mode regulated by the cytoskeleton and ubiquitin dependent processes. Here we show that that such a heterologous prion induction is due to the ability of Lsb2 to form a transient prion state, generated in response to thermal stress. Evolutionary acquisition of prion-inducing activity by Lsb2 is traced to a single amino acid change, coinciding with the acquisition of thermotolerance in the Saccharomyces yeast lineage. This raises the intriguing possibility that the transient prion formation could aid in functioning of Lsb2 at higher temperatures. Prions are transmissible protein aggregates. Chernova et al. show that a transient prion of yeast short-lived cytoskeletal protein Lsb2 is triggered by thermal stress and induces other prions. Evolutionary acquisition of prion-inducing activity by Lsb2 is traced to a single amino acid substitution, coinciding with yeast adaptation to higher temperatures.