Supporting the structural basis of prion strains: Induction and identification of [PSI] variants
Supporting the structural basis of prion strains: Induction and identification of [PSI] variants
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DOI：
10.1006/jmbi.2001.4542
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发表时间：
2001-04-13
影响因子：
5.6
通讯作者：
King, CY
中科院分区：
文献类型：
--
作者：
King, CY
[PSI]遗传元件，其增强酵母酿酒酵母中的无义抑制效率，被认为是Sup 35蛋白的淀粉样聚集体，并通过朊病毒样机制自我繁殖。类似于哺乳动物朊病毒的菌株，具有不同的无义抑制效率和有丝分裂稳定性的[PSI]的变体可以从相同的酵母遗传背景中分离。在“纯蛋白质”假说的框架下，朊病毒的变体被认为是同一朊病毒多肽的不同构象异构体。本研究旨在为[PSI]变异的结构基础提供进一步的支持。[PSI]的三种变体通过Sup 35蛋白的一组11个单点突变来诱导和区分。变异的表型与[PSI]元素本质上相关，推测结构上不同的淀粉样蛋白，而不是由遗传背景的变异产生的。差异纳入[PSI]变体的Sup 35点突变以及N和C-末端截短的Sup 35片段在体内进一步证明，表明不同的补丁的氨基酸残基参与组装[PSI]变体。这些结果建立了[PSI]变体分型的方法，并表明淀粉样蛋白结构的遗传变异可以来自相同的多肽。(C)北京：科学出版社.
The [PSI] genetic element, which enhances the nonsense suppression efficiency in the yeast Saccharomyces cerevisiae, is thought to be amyloid-like aggregates of the Sup35 protein, and to self-propagate by a prion-like mechanism. Analogous to strains of the mammalian prion, variants of [PSI], with different nonsense suppression efficiencies and mitotic stabilities, can be isolated from the same yeast genetic background. Ln the framework of the "protein-only" hypothesis, variants of prion are assumed to be distinct conformers of the same prion polypeptide. This study aims to provide further support for the structural basis of [PSI] variation. Three variants of [PSI] were induced and distinguished by a panel of 11 single point mutations of the Sup35 protein. The variant phenotypes are intrinsically associated with [PSI] elements, presumably structurally different amyloids, rather than produced from variations in the genetic background. Differential incorporation to [PSI] variants of a Sup35 point mutation as well as N and C-terminally truncated Sup35 fragments is further demonstrated in vivo, suggesting that distinct patches of amino acid residues are involved in the assembly of [PSI] variants. These results establish a method for [PSI] variant-typing and indicate that heritable variations of amyloid structures can be derived from the same polypeptide. (C) 2001 Academic Press.