Model for disordered proteins with strongly sequence-dependent liquid phase behavior
Model for disordered proteins with strongly sequence-dependent liquid phase behavior
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DOI：
10.1101/864942
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
A. Statt;Helena Casademunt;C. Brangwynne;A. Panagiotopoulos
中科院分区：
文献类型：
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作者：
A. Statt;Helena Casademunt;C. Brangwynne;A. Panagiotopoulos
本质无序蛋白质的相分离对于无膜细胞器或生物分子凝聚物的形成是重要的，其在细胞内的生化过程的调节中起关键作用。在这项工作中，我们研究了本质无序蛋白质的粗粒度模型的不同序列的相分离，并发现了令人惊讶的丰富的相行为。我们研究了总疏水部分的分数和疏水部分的分布。毫不奇怪，具有较大疏水部分的序列显示出常规的液-液相分离。的临界点的位置系统的终端珠的序列的影响，由于界面组成和张力的变化。对于具有较低疏水性的序列，我们不仅观察到常规的液-液相分离，而且还观察到重入相行为，其中液相密度在较低温度下降低。对于某些序列，我们观察到由聚集体组成的开放相的形成，而不是正常的液体。这些聚集体的整体密度低于传统的液相，并表现出复杂的几何形状与大的相互连接的弦状或膜状集群。我们的研究结果表明，在残基的顺序微小的改变可能会导致蛋白质的相行为的大的变化，一个重要的生物学潜在的相关性的事实。
Phase separation of intrinsically disordered proteins is important for the formation of membraneless organelles, or biomolecular condensates, which play key roles in the regulation of biochemical processes within cells. In this work, we investigated the phase separation of different sequences of a coarse-grained model for intrinsically disordered proteins and discovered a surprisingly rich phase behavior. We studied both the fraction of total hydrophobic parts and the distribution of hydrophobic parts. Not surprisingly, sequences with larger hydrophobic fractions showed conventional liquid-liquid phase separation. The location of the critical point was systematically influenced by the terminal beads of the sequence, due to changes in interfacial composition and tension. For sequences with lower hydrophobicity, we observed not only conventional liquid-liquid phase separation, but also reentrant phase behavior, in which the liquid phase density decreases at lower temperatures. For some sequences, we observed formation of open phases consisting of aggregates, rather than a normal liquid. These aggregates had overall lower densities than the conventional liquid phases, and exhibited complex geometries with large interconnected string-like or membrane-like clusters. Our findings suggest that minor alterations in the ordering of residues may lead to large changes in the phase behavior of the protein, a fact of significant potential relevance for biology.