The effects of amino acid composition of glutamine-rich domains on amyloid formation and fragmentation.
The effects of amino acid composition of glutamine-rich domains on amyloid formation and fragmentation.
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DOI：
10.1371/journal.pone.0046458
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kushnirov VV
中科院分区：
文献类型：
--
作者：
Alexandrov AI;Polyanskaya AB;Serpionov GV;Ter-Avanesyan MD;Kushnirov VV
蛋白伴侣Hsp 104使淀粉样蛋白聚合物断裂，使其在酵母中作为朊病毒繁殖。决定断裂频率的因素尚不清楚，尽管通常认为它取决于朊病毒聚合物的物理强度。具有长聚谷氨酰胺延伸的蛋白质代表了揭示酵母中聚合物片段化所需的序列元件的易于处理的模型，因为它们形成片段化较差的淀粉样蛋白。在这里，我们表明，散布的多聚谷氨酰胺伸展与各种氨基酸残基的差异影响在体内形成和分裂的各自的淀粉样蛋白。芳香族残基酪氨酸，色氨酸和苯丙氨酸强烈刺激聚合物断裂，导致小的二聚体的低聚物的外观。丙氨酸、蛋氨酸、半胱氨酸、丝氨酸、苏氨酸和组氨酸也增强片段化，而带电残基、脯氨酸、甘氨酸和亮氨酸抑制聚合。我们的数据表明，碎片化频率主要取决于识别的碎片促进残基的热休克蛋白104和/或其共分子伴侣，而不是对聚合物的物理稳定性。这表明这些残基与分子伴侣的差异暴露定义了朊病毒变体特异性聚合物片段化效率的差异。
Fragmentation of amyloid polymers by the chaperone Hsp104 allows them to propagate as prions in yeast. The factors which determine the frequency of fragmentation are unclear, though it is often presumed to depend on the physical strength of prion polymers. Proteins with long polyglutamine stretches represent a tractable model for revealing sequence elements required for polymer fragmentation in yeast, since they form poorly fragmented amyloids. Here we show that interspersion of polyglutamine stretches with various amino acid residues differentially affects the in vivo formation and fragmentation of the respective amyloids. Aromatic residues tyrosine, tryptophan and phenylalanine strongly stimulated polymer fragmentation, leading to the appearance of oligomers as small as dimers. Alanine, methionine, cysteine, serine, threonine and histidine also enhanced fragmentation, while charged residues, proline, glycine and leucine inhibited polymerization. Our data indicate that fragmentation frequency primarily depends on the recognition of fragmentation-promoting residues by Hsp104 and/or its co-chaperones, rather than on the physical stability of polymers. This suggests that differential exposure of such residues to chaperones defines prion variant-specific differences in polymer fragmentation efficiency.
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影响因子：
4.8
作者：
Alexandrov, Ilya M.;Vishnevskaya, Aleksandra B.;Ter-Avanesyan, Michael D.;Kushnirov, Vitaly V.
通讯作者：
Kushnirov, Vitaly V.
影响因子：
3
作者：
Goldsbury, Claire;Baxa, Ulrich;Simon, Martha N.;Steven, Alasdair C.;Engel, Andreas;Wall, Joseph S.;Aebi, Ueli;Mueller, Shirley A.
通讯作者：
Mueller, Shirley A.
影响因子：
4.8
作者：
Lum, R;Tkach, JM;Glover, JR
通讯作者：
Glover, JR
影响因子：
64.8
作者：
Tanaka, M;Chien, P;Weissman, JS
通讯作者：
Weissman, JS
影响因子：
4.8
作者：
Helsen, Christopher W.;Glover, John R.
通讯作者：
Glover, John R.