Hsp40 function in yeast prion propagation: Amyloid diversity necessitates chaperone functional complexity.
Hsp40 function in yeast prion propagation: Amyloid diversity necessitates chaperone functional complexity.
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DOI：
10.1080/19336896.2015.1020268
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发表时间：
2015
期刊：
影响因子：
2.3
通讯作者：
Hines JK
中科院分区：
文献类型：
--
作者：
Sporn ZA;Hines JK
酵母朊病毒是可遗传的基于蛋白质的元素，其中大多数是由淀粉样蛋白聚集体形成的，依赖于分子伴侣的作用来传递给后代。朊病毒可以形成独特的淀粉样蛋白结构，在哺乳动物系统中被称为“菌株”，它决定了病理进展和跨物种感染障碍。在酵母中，这些相同的淀粉样蛋白结构多态性，称为“变体”，决定了朊病毒相关表型的强度和有丝分裂的稳定性。我们最近报道了[PSI+]朊病毒变体对Hsp40/ j蛋白Sis1的基本结构域要求不同，这在2种不同的酵母朊病毒之间是互斥的，表明Sis1具有功能多元性。在这里，我们扩展了该分析，纳入了额外的数据，这些数据共同支持Sis1具有多种功能角色的假设，这些功能角色可以通过不同的域集来完成。不同的朊病毒和朊病毒变体对这些功能的要求不同。我们还提供了关于hsp104介导的朊病毒消除的新数据，并表明Sis1的一些功能，但不是全部，在人类同源物Hdj1/DNAJB1中是保守的。重要的是，迄今为止在酿酒酵母中发现的10种淀粉样蛋白朊病毒中，只有4种对伴侣蛋白的需求是已知的，这使得淀粉样蛋白结构的多样性以及淀粉样蛋白-伴侣蛋白相互作用的可能模式在很大程度上未被探索。
Yeast prions are heritable protein-based elements, most of which are formed of amyloid aggregates that rely on the action of molecular chaperones for transmission to progeny. Prions can form distinct amyloid structures, known as ‘strains’ in mammalian systems, that dictate both pathological progression and cross-species infection barriers. In yeast these same amyloid structural polymorphisms, called ‘variants’, dictate the intensity of prion-associated phenotypes and stability in mitosis. We recently reported that [PSI+] prion variants differ in the fundamental domain requirements for one chaperone, the Hsp40/J-protein Sis1, which are mutually exclusive between 2 different yeast prions, demonstrating a functional plurality for Sis1. Here we extend that analysis to incorporate additional data that collectively support the hypothesis that Sis1 has multiple functional roles that can be accomplished by distinct sets of domains. These functions are differentially required by distinct prions and prion variants. We also present new data regarding Hsp104-mediated prion elimination and show that some Sis1 functions, but not all, are conserved in the human homolog Hdj1/DNAJB1. Importantly, of the 10 amyloid-based prions indentified to date in Saccharomyces cerevisiae, the chaperone requirements of only 4 are known, leaving a great diversity of amyloid structures, and likely modes of amyloid-chaperone interaction, largely unexplored.