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Prion and nonprion amyloids: a comparison inspired by the yeast Sup35 protein.
Prion ( IF 1.9 ) Pub Date : 2007-07-06 , DOI: 10.4161/pri.1.3.4840
Vitaly V Kushnirov 1 , Aleksandra B Vishnevskaya , Ilya M Alexandrov , Michael D Ter-Avanesyan
Affiliation  

Yeast prion determinants are related to polymerization of some proteins into amyloid-like fibers. The [PSI(+)] determinant reflects polymerization of the Sup35 protein. Fragmentation of prion polymers by the Hsp104 chaperone represents a key step of the prion replication cycle. The frequency of fragmentation varies depending on the structure of the prion polymers and defines variation in the prion phenotypes, e.g., the suppressor strength of [PSI(+)] and stability of its inheritance. Besides [PSI(+)], overproduction of Sup35 can produce nonheritable phenotypically silent Sup35 amyloid-like polymers. These polymers are fragmented poorly and are present due to efficient seeding with the Rnq1 prion polymers, which occurs by several orders of magnitude more frequently than seeding of [PSI(+)] appearance. Such Sup35 polymers resemble human nonprion amyloids by their nonheritability, mode of appearance and increased size. Thus, a single protein, Sup35, can model both prion and nonprion amyloids. In yeast, these phenomena are distinguished by the frequency of polymer fragmentation. We argue that in mammals the fragmentation frequency also represents a key factor defining differing properties of prion and nonprion amyloids, including infectivity. By analogy with the Rnq1 seeding of nonheritable Sup35 polymers, the "species barrier" in prion transmission may be due to seeding by heterologous prion of nontransmissible type of amyloid, rather than due to the lack of seeding.

中文翻译:

朊病毒和非朊病毒淀粉样蛋白:受酵母 Sup35 蛋白启发的比较。

酵母朊病毒决定簇与一些蛋白质聚合成淀粉样蛋白纤维有关。[PSI(+)] 决定簇反映了 Sup35 蛋白的聚合。Hsp104 分子伴侣对朊病毒聚合物的断裂代表了朊病毒复制周期的关键步骤。断裂频率根据朊病毒聚合物的结构而变化,并定义了朊病毒表型的变化,例如,[PSI(+)]的抑制强度及其遗传的稳定性。除了[PSI(+)]之外,Sup35的过量产生还可以产生不可遗传的表型沉默的Sup35淀粉样蛋白样聚合物。这些聚合物的破碎性很差,并且由于 Rnq1 朊病毒聚合物的有效播种而存在,其发生频率比 [PSI(+)] 出现的播种频率高几个数量级。此类 Sup35 聚合物在非遗传性、外观模式和增大的尺寸方面类似于人类非朊病毒淀粉样蛋白。因此,单一蛋白质 Sup35 可以模拟朊病毒和非朊病毒淀粉样蛋白。在酵母中,这些现象通过聚合物断裂的频率来区分。我们认为,在哺乳动物中,碎片频率也是定义朊病毒和非朊病毒淀粉样蛋白不同特性(包括感染性)的关键因素。通过与非遗传性 Sup35 聚合物的 Rnq1 播种进行类比,朊病毒传播中的“物种屏障”可能是由于非传播型淀粉样蛋白的异源朊病毒播种,而不是由于缺乏播种。
更新日期:2019-11-01
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