Not too sticky There is increasing evidence for a role of liquid-liquid phase separation (LLPS) in many cellular processes. Many proteins that undergo LLPS include prionlike domains (PLDs), which are enriched in polar amino acids and often interspersed with aromatic residues. Combining experimental data with simulations, Martin et al. quantified concentrations of PLDs in coexisting dilute and dense phases as a function of temperature and show that the phase behavior is determined by the number of aromatic residues and their patterning, with uniform patterning of aromatic residues promoting LLPS and inhibiting aggregation. They developed a sticker-and-spacers model that can predict the phase behavior of PLDs on the basis of their sequence. Science, this issue p. 694 A stickers-and-spacers model reproduces experimentally measured sequence-specific phase diagrams of prion-like domains. Prion-like domains (PLDs) can drive liquid-liquid phase separation (LLPS) in cells. Using an integrative biophysical approach that includes nuclear magnetic resonance spectroscopy, small-angle x-ray scattering, and multiscale simulations, we have uncovered sequence features that determine the overall phase behavior of PLDs. We show that the numbers (valence) of aromatic residues in PLDs determine the extent of temperature-dependent compaction of individual molecules in dilute solutions. The valence of aromatic residues also determines full binodals that quantify concentrations of PLDs within coexisting dilute and dense phases as a function of temperature. We also show that uniform patterning of aromatic residues is a sequence feature that promotes LLPS while inhibiting aggregation. Our findings lead to the development of a numerical stickers-and-spacers model that enables predictions of full binodals of PLDs from their sequences.

中文翻译：

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芳香族残基的化合价和图案决定了类朊病毒结构域的相行为

不太粘稠 越来越多的证据表明液-液相分离 (LLPS) 在许多细胞过程中发挥着重要作用。许多经历 LLPS 的蛋白质都包含朊病毒结构域 (PLD)，这些结构域富含极性氨基酸，并且通常散布有芳香族残基。Martin 等人将实验数据与模拟相结合。定量共存的稀相和密相中 PLD 的浓度作为温度的函数，并表明相行为由芳香族残基的数量及其图案决定，芳香族残基的均匀图案促进 LLPS 并抑制聚集。他们开发了一种贴纸和垫片模型，可以根据 PLD 的序列预测其相行为。科学，本期第 14 页。第694章 贴纸和间隔物模型再现了实验测量的朊病毒结构域的序列特异性相图。朊病毒样结构域 (PLD) 可以驱动细胞中的液-液相分离 (LLPS)。使用包括核磁共振波谱、小角度 X 射线散射和多尺度模拟在内的综合生物物理方法，我们发现了决定 PLD 整体相行为的序列特征。我们表明，PLD 中芳香族残基的数量（化合价）决定了稀溶液中单个分子的温度依赖性压缩程度。芳香族残基的化合价还决定了完整的双节线，该双节线可量化共存的稀相和密相中 PLD 的浓度，作为温度的函数。我们还表明，芳香族残基的均匀图案是促进 LLPS 同时抑制聚集的序列特征。我们的发现导致了数值贴纸和间隔模型的开发，该模型能够根据 PLD 的序列预测 PLD 的完整双节线。