Investigating protein conformation-based inheritance and disease in yeast
Investigating protein conformation-based inheritance and disease in yeast
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DOI：
10.1098/rstb.2000.0762
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发表时间：
2001-02-28
期刊：
影响因子：
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通讯作者：
Sondheimer, N
中科院分区：
文献类型：
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作者：
Lindquist, S;Krobitsch, S;Sondheimer, N
我们的工作支持蛋白质可以作为遗传因素的假设。这种仅蛋白质的遗传机制的传播方式与海绵状脑病中仅蛋白质的传染源的传播假设大致相同;因此这些蛋白质因子被称为酵母朊病毒。我们的工作重点是[PSI+]，这是一种改变翻译保真度的主导细胞质遗传因子。这种翻译的变化是由抑制-终止因子Sup 35的构象的自我永久变化产生的。最近，我们已经确定，基因遗传的新元素可以通过故意的基因工程创造，为操纵遗传的新方法开辟了前景。我们还发现了其他以前未知的蛋白质遗传元素在酵母基因组中编码的证据。最后，我们已经开始使用酵母作为研究人类蛋白质折叠疾病的模型系统，例如亨廷顿氏病。导致这些疾病的蛋白质与产生基于蛋白质的遗传机制的蛋白质具有惊人的相似性。
Our work supports the hypothesis that a protein can serve as an element of genetic inheritance. This protein-only mechanism of inheritance is propagated in much the same way as hypothesized for the transmission of the protein-only infectious agent in the spongiform encephalopathies; hence these protein factors have been called yeast prions. Our work has focused on [PSI+], a dominant cytoplasmically inherited factor that alters translational fidelity. This change in translation is produced by a self-perpetuating change in the conformation of the translation-termination factor, Sup35. Most recently, we have determined that new elements of genetic inheritance can be created by deliberate genetic engineering, opening prospects for new methods of manipulating heredity. We have also uncovered evidence that other previously unknown elements of protein-based inheritance are encoded in the yeast genome. finally, we have begun to use yeast as a model system for studying human protein folding diseases, such as Huntington's disease. Proteins responsible for some of these diseases have properties uncannily similar to those that produce protein-based mechanisms of inheritance.