"Prion-proof" for [PIN+]:: Infection with in vitro-made amyloid aggregates of Rnq1p-(132-405) induces [PIN+]
"Prion-proof" for [PIN+]:: Infection with in vitro-made amyloid aggregates of Rnq1p-(132-405) induces [PIN+]
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DOI：
10.1016/j.jmb.2006.10.069
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发表时间：
2007-01-19
影响因子：
5.6
通讯作者：
Liebman, Susan W.
中科院分区：
文献类型：
--
作者：
Patel, Basant K.;Liebman, Susan W.
朊病毒是自我繁殖的感染性蛋白质构象。哺乳动物朊病毒，PrPSc，负责神经退行性疾病，如牛海绵状脑病（疯牛病）和克雅氏病，似乎是PrPc的富含β折叠的淀粉样蛋白构象，将PrPc转化为PrPSc。然而，一个明确的证明“蛋白质只有”感染的PrPSc仍然缺乏。到目前为止，已经证明了三种朊病毒（[PSI+]，[URE 3]和[Het-s]）的蛋白质感染，所有这些都是真菌来源的。相当多的证据支持另一种蛋白质，酵母Rnq 1 p，可以形成朊病毒[PIN+]的假设。虽然Rnq 1 p在朊病毒化后不会失去任何已知的功能，但[PIN+]具有有趣的正表型：促进其他朊病毒的出现和不稳定。以及亨廷顿蛋白的多聚谷氨酰胺延伸的聚集。在这里，我们将富含Gln/Asn的Rnq 1 p重组片段转化为富含β折叠的淀粉样聚集体。虽然用于[PSI+]和[URE 3]感染性测定的方法没有产生Rnq 1 p聚集体的仅蛋白质感染，但我们通过修改方案成功获得了仅蛋白质感染。这项工作证明了[PIN+]是由Rnq 1 p的淀粉样聚集体介导的朊病毒，并支持异源朊病毒通过其淀粉样区域的相互作用影响彼此的外观和繁殖的假设。(c)2006年由Elsevier Ltd.出版
Prions are self-propagating, infectious protein conformations. The mammalian prion, PrPSc, responsible for neurodegenerative diseases like bovine spongiform encephalopathy (BSE; "mad cow" disease) and Creutzfeldt-Jakob's disease, appears to be a beta-sheet-rich amyloid conformation of PrPc that converts PrPc into PrPSc. However, an unequivocal demonstration of "protein-only" infection by PrPSc is still lacking. So far, protein only infection has been proven for three prions, [PSI+], [URE3] and [Het-s], all of fungal origin. Considerable evidence supports the hypothesis that another protein, the yeast Rnq1p, can form a prion, [PIN+]. While Rnq1p does not lose any known function upon prionization, [PIN+] has interesting positive phenotypes: facilitating the appearance and destabilization of other prions. as well as the aggregation of polyglutamine extensions of the Huntingtin protein. Here, we polymerize a Gln/Asn-rich recombinant fragment of Rnq1p into beta-sheet-rich amyloid-like aggregates. While the method used for [PSI+] and [URE3] infectivity assays did not yield protein-only infection for the Rnq1p aggregates, we did successfully obtain protein-only infection by modifying the protocol. This work proves that [PIN+] is a prion mediated by amyloid-like aggregates of Rnq1p, and supports the hypothesis that heterologous prions affect each other's appearance and propagation through interaction of their amyloid-like regions. (c) 2006 Published by Elsevier Ltd.