Alternative assembly pathways of the amyloidogenic yeast prion determinant Sup35-NM
Alternative assembly pathways of the amyloidogenic yeast prion determinant Sup35-NM
复制标题
DOI：
10.1038/sj.embor.7401096
复制
发表时间：
2007-12-01
期刊：
影响因子：
7.7
通讯作者：
Scheibel, Thomas
中科院分区：
文献类型：
--
作者：
Hess, Simone;Lindquist, Susan L.;Scheibel, Thomas
翻译终止因子Sup35的自我永久构象变化与酿酒酵母的朊病毒现象有关。在体外，Sup35的朊病毒决定区（NM）通过成核构象转换的机制组装成淀粉样纤维。在这里，我们描述了NM的另一种组装途径，该途径产生由B链和随机卷曲区域组成的细丝，其直径比淀粉样纤维小几倍。NM细丝用硫磺素T或刚果红都检测不到，并且不显示SDS或蛋白酶抗性。由于纤维丝不能自我转化为纤维，也不能作为种子，因此它们不是淀粉样纤维形成的中间体。相反，它们代表稳定的非途径形式。类似于哺乳动物朊病毒蛋白，Sup35含有位于NM区域的寡肽重复序列。我们发现重复序列的数量决定了蛋白质在纤维和淀粉样纤维之间的分配。低重复数有利于丝状结构的形成，而高重复数有利于淀粉样纤维的形成。
The self-perpetuating conformational change of the translation termination factor Sup35 is associated with a prion phenomenon of Saccharomyces cerevisiae. In vitro, the prion-determining region (NM) of Sup35 assembles into amyloid-like fibres through a mechanism of nucleated conformational conversion. Here, we describe an alternative assembly pathway of NM that produces filaments that are composed of b-strands and random coiled regions with several-fold smaller diameters than the amyloid fibres. NM filaments are not detectable with either thioflavin T or Congo Red and do not show SDS or protease resistance. As filaments do not self-convert into fibres and do not act as seed, they are not intermediates of amyloid fibre formation. Instead, they represent a stable off-pathway form. Similar to mammalian prion proteins, Sup35 contains oligopeptide repeats located in the NM region. We found that the number of repeats determines the partitioning of the protein between filaments and amyloid-like fibres. Low numbers of repeats favour the formation of the filamentous structure, whereas high numbers of repeats favour the formation of amyloid-like fibres.