Strains of [PSI+] are distinguished by their efficiencies of prion-mediated conformational conversion
Strains of [PSI+] are distinguished by their efficiencies of prion-mediated conformational conversion
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DOI：
10.1093/emboj/20.22.6236
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发表时间：
2001-11-15
期刊：
影响因子：
11.4
通讯作者：
Lindquist, S
中科院分区：
文献类型：
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作者：
Uptain, SM;Sawicki, GJ;Lindquist, S
酵母朊病毒是基于蛋白质的遗传元件，其通过蛋白质构象的自我永久变化产生表型。对于朊病毒[PSI+]，该蛋白是Sup35，其由融合到翻译终止区的朊病毒决定区（NM）组成。[PSI具有不同的可遗传的翻译终止缺陷（弱或强）的菌株（变体）可以存在于相同的遗传背景中。[PSI+]变体使人联想到哺乳动物朊病毒株，其可以在相同的小鼠株中传代，但具有不同的疾病潜伏期和脑病理。我们发现[PSI+]变体在朊病毒和非朊病毒状态下含有不同比例的Sup35，这与不同的翻译终止效率相关。事实上，来自强[PSI+]变体的Sup35的部分纯化的朊病毒形式比几种弱变体更有效地转化纯化的NM。然而，这种差异在第二轮体外转化中丢失。因此，[PSI+]变体是由朊病毒介导的转化效率的差异引起的，并且[PSI+]变体的维持不仅仅涉及到单独向NM的有核构象转化（模板化）。
Yeast prions are protein-based genetic elements that produce phenotypes through self-perpetuating changes in protein conformation. For the prion [PSI+] this protein is Sup35, which is comprised of a prion-determining region (NM) fused to a translational termination region. [PSI+] strains (variants) with different heritable translational termination defects (weak or strong) can exist in the same genetic background. [PSI+] variants are reminiscent of mammalian prion strains, which can be passaged in the same mouse strain yet have different disease latencies and brain pathologies. We found that [PSI+] variants contain different ratios of Sup35 in the prion and non-prion state that correlate with different translation termination efficiencies. Indeed, the partially purified prion form of Sup35 from a strong [PSI+] variant converted purified NM much more efficiently than that of several weak variants. However, this difference was lost in a second round of conversion in vitro. Thus, [PSI+] variants result from differences in the efficiency of prion-mediated conversion, and the maintenance of [PSI+] variants involves more than nucleated conformational conversion (templating) to NM alone.