Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics
Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics
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DOI：
10.1016/j.chembiol.2013.12.013
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发表时间：
2014-02-20
影响因子：
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通讯作者：
Lindquist, Susan
中科院分区：
文献类型：
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作者：
Frederick, Kendra K.;Debelouchina, Galia T.;Lindquist, Susan
酵母朊病毒是一种基于蛋白质的自模板遗传机制，其构象变化导致获得多种新的表型。其中最好的研究是Sup35的朊病毒结构域（NM），它形成一种淀粉样蛋白，可以采用几种不同的构象（菌株），产生不同的表型。使用魔角自旋核磁共振光谱，我们提供了一个详细的看看这些形式的动态特性在广泛的时间尺度。我们确定不同的朊病毒株具有不同的淀粉样结构，在不同的化学环境中具有许多侧链。令人惊讶的是，具有较大比例的刚性残基的朊病毒菌株也具有较大比例的高度移动的残基。迁移率的差异与体内朊病毒分配因子Hsp104相互作用的差异相关，这可能解释了菌株特异性遗传差异。
Yeast prions are self-templating protein-based mechanisms of inheritance whose conformational changes lead to the acquisition of diverse new phenotypes. The best studied of these is the prion domain (NM) of Sup35, which forms an amyloid that can adopt several distinct conformations (strains) that produce distinct phenotypes. Using magic-angle spinning nuclear magnetic resonance spectroscopy, we provide a detailed look at the dynamic properties of these forms over a broad range of time-scales. We establish that different prion strains have distinct amyloid structures, with many side chains in different chemical environments. Surprisingly, the prion strain with a larger fraction of rigid residues also has a larger fraction of highly mobile residues. Differences in mobility correlate with differences in interaction with the prion-partitioning factor Hsp104 in vivo, perhaps explaining strain-specific differences in inheritance.