Atomic structures of low-complexity protein segments reveal kinked β sheets that assemble networks.

Atomic structures of low-complexity protein segments reveal kinked β sheets that assemble networks.
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低复杂性蛋白段的原子结构揭示了组装网络的扭结β薄片。

DOI:
10.1126/science.aan6398
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发表时间:
2018-02-09
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Eisenberg DS
Eisenberg DS
中科院分区:
其他
文献类型:
--
作者:
Hughes MP;Sawaya MR;Boyer DR;Goldschmidt L;Rodriguez JA;Cascio D;Chong L;Gonen T;Eisenberg DS

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亚细胞无膜组装是生物学中一个重新焕发活力的领域,对这些组装中低复杂性蛋白质结构域之间的作用力进行了热烈的科学讨论。为了阐明这些力量,我们确定了与无膜组件相关的蛋白质低复杂性结构域的五个片段的原子结构。它们的共同结构特征是片段堆叠成扭结的β-片层,β-片层配对成原丝。与淀粉样纤维的空间拉链不同,扭结片通过极性原子和芳香侧链相互作用很弱。通过在我们的扭结结构上计算人类蛋白质组,我们确定了数百个可能能够形成这种相互作用的低复杂性片段。这些片段存在于多种蛋白质中,如RNA结合剂、核孔蛋白和角蛋白,已知它们形成网络并定位于无膜组装体。穿线揭示了人类蛋白质组中数百个能够形成扭结多价原丝的低复杂性片段。
Subcellular membrane-less assemblies are a reinvigorated area study in biology with spirited scientific discussions on the forces between the low-complexity protein domains within these assemblies. To illuminate these forces we determined atomic structures of five segments of protein low-complexity domains associated with membrane-less assemblies. Their common structural feature is the stacking of segments into kinked β-sheets which pair into protofilaments. Unlike steric zippers of amyloid fibrils, the kinked sheets interact weakly through polar atoms and aromatic sidechains. By computationally threading the human proteome on our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, and keratins, known to form networks and localize to membrane-less assemblies. Threading reveals hundreds of low-complexity segments in the human proteome capable of forming kinked multivalent protofilaments.
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