Phase separation of a yeast prion protein promotes cellular fitness
Phase separation of a yeast prion protein promotes cellular fitness
复制标题
DOI：
10.1126/science.aao5654
复制
发表时间：
2018-01-05
期刊：
影响因子：
56.9
通讯作者：
Alberti, Simon
中科院分区：
文献类型：
--
作者：
Franzmann, Titus M.;Jahnel, Marcus;Alberti, Simon
尽管朊病毒结构域在神经退行性疾病中发挥重要作用，但其生理功能仍然是个谜。先前对酵母朊病毒的研究已经将朊病毒结构域定义为形成自繁殖聚集体的序列。在这里，我们发现了一个意想不到的功能的典型酵母朊病毒蛋白Sup 35。在应激条件下，Sup 35通过pH调节的液体样相分离随后凝胶化形成保护性凝胶。相分离由N-末端朊病毒结构域介导，并由相邻的pH传感器结构域调节。相分离促进酵母细胞的生存拯救的重要Sup 35翻译因子从应力诱导的损害。因此，朊病毒样结构域代表保守的环境应激传感器，通过改变蛋白质相行为促进在不稳定环境中的快速适应。
Despite the important role of prion domains in neurodegenerative disease, their physiological function has remained enigmatic. Previous work with yeast prions has defined prion domains as sequences that form self-propagating aggregates. Here, we uncovered an unexpected function of the canonical yeast prion protein Sup35. In stressed conditions, Sup35 formed protective gels via pH-regulated liquid-like phase separation followed by gelation. Phase separation was mediated by the N-terminal prion domain and regulated by the adjacent pH sensor domain. Phase separation promoted yeast cell survival by rescuing the essential Sup35 translation factor from stress-induced damage. Thus, prion-like domains represent conserved environmental stress sensors that facilitate rapid adaptation in unstable environments by modifying protein phase behavior.