Appearance and propagation of polyglutamine-based amyloids in yeast: tyrosine residues enable polymer fragmentation.
Appearance and propagation of polyglutamine-based amyloids in yeast: tyrosine residues enable polymer fragmentation.
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DOI：
10.1074/jbc.m802071200
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发表时间：
2008-05-30
影响因子：
4.8
通讯作者：
Kushnirov, Vitaly V.
中科院分区：
文献类型：
--
作者：
Alexandrov, Ilya M.;Vishnevskaya, Aleksandra B.;Ter-Avanesyan, Michael D.;Kushnirov, Vitaly V.
在酵母中，Hsp104分子伴侣使淀粉样蛋白聚合物断裂，使它们能够作为朊病毒繁殖。酵母Sup35蛋白的朊病毒形成结构域富含谷氨酰胺、天冬酰胺、酪氨酸和甘氨酸残基，这些残基可限定其朊病毒性质。长的多聚谷氨酰胺片段也可以驱动酵母中的淀粉样蛋白聚合，但这些聚合物由于片段化差而无法繁殖，并且通过与Rnq 1朊病毒聚合物的恒定接种而存在。我们提出，聚谷氨酰胺淀粉样蛋白的片段化可以通过将疏水性氨基酸残基掺入聚谷氨酰胺片段中来改善。为了研究这一点，我们构建了一套多聚谷氨酰胺与或不与非朊病毒结构域的Sup35融合的酪氨酸延伸。这些嵌合体的聚合迅速开始，其效率随着拉伸尺寸而增加。多聚谷氨酰胺的蛋白质聚合延伸短于70个残基需要Rnq1朊病毒种子。具有较长延伸的蛋白质独立于Rnq1聚合，因此可以繁殖。酪氨酸内的聚谷氨酰胺伸展的存在下，显着增强聚合物的碎片，并允许聚合物的繁殖在Rnq1的情况下，在某些情况下，HSP 104。
In yeast, fragmentation of amyloid polymers by the Hsp104 chaperone allows them to propagate as prions. The prion-forming domain of the yeast Sup35 protein is rich in glutamine, asparagine, tyrosine, and glycine residues, which may define its prion properties. Long polyglutamine stretches can also drive amyloid polymerization in yeast, but these polymers are unable to propagate because of poor fragmentation and exist through constant seeding with the Rnq1 prion polymers. We proposed that fragmentation of polyglutamine amyloids may be improved by incorporation of hydrophobic amino acid residues into polyglutamine stretches. To investigate this, we constructed sets of polyglutamine with or without tyrosine stretches fused to the non-prion domains of Sup35. Polymerization of these chimeras started rapidly, and its efficiency increased with stretch size. Polymerization of proteins with polyglutamine stretches shorter than 70 residues required Rnq1 prion seeds. Proteins with longer stretches polymerized independently of Rnq1 and thus could propagate. The presence of tyrosines within polyglutamine stretches dramatically enhanced polymer fragmentation and allowed polymer propagation in the absence of Rnq1 and, in some cases, of Hsp104.