美国圣裘德儿童研究医院Tanja Mittag和美国华盛顿大学Rohit V. Pappu研究团队合作发现芳香族残基的化合价和模式决定了病毒样结构域（PLD）的相行为。相关论文于2020年2月7日发表在《科学》上。

使用包括核磁共振波谱、小角X射线散射和大规模模拟在内的综合生物物理方法，他们发现确定PLD整体相位行为的序列特征。他们表明，PLD中芳香族残基的数量（价）决定了稀溶液中各个分子的温度依赖性压缩程度。芳香族残基的化合价也确定了完整的二元坐标，该二元坐标可量化随温度变化而存在的稀相和致密相中PLD的浓度。他们还表明，芳香族残基的同一模式是一个序列特征，可在抑制聚集的同时促进液相-液相分离（LLPS）。他们的发现导致了一系列贴纸和垫片模型的发展，该模型能够根据其序列预测PLD的完整二元线。

据了解，PLD可以驱动细胞内的LLPS。

附：英文原文

Title: Valence and patterning of aromatic residues determine the phase behavior of prion-like domains

Author: Erik W. Martin, Alex S. Holehouse, Ivan Peran, Mina Farag, J. Jeremias Incicco, Anne Bremer, Christy R. Grace, Andrea Soranno, Rohit V. Pappu, Tanja Mittag

Issue&Volume: 2020/02/07

Abstract: 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.

DOI: 10.1126/science.aaw8653

Source: https://science.sciencemag.org/content/367/6478/694