Microphase Separation Produces Interfacial Environment within Diblock Biomolecular Condensates.
Microphase Separation Produces Interfacial Environment within Diblock Biomolecular Condensates.
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微相分离在二嵌段生物分子缩合物内产生界面环境。
DOI：
10.1101/2023.03.30.534967
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Zhang,Bin
中科院分区：
文献类型：
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作者：
Latham,AndrewP;Zhu,Longchen;Sharon,DinaA;Ye,Songtao;Willard,AdamP;Zhang,Xin;Zhang,Bin
内在无序蛋白质的相分离正成为细胞组织的重要机制。然而，由于缺乏探测高分辨率结构细节的有效方法，将蛋白质序列与凝聚物的物理性质（即分子语法）联系起来的努力受到阻碍。利用多尺度模拟和荧光寿命成像显微镜实验相结合，我们系统地探索了一系列由双块弹性蛋白样多肽（ELPs）组成的系统。模拟成功地再现了氨基酸取代后凝聚态稳定性的变化，并揭示了单一凝聚态内不同的微环境，我们用环境敏感的荧光团验证了这一点。亲疏水残基的分散和二级结构的缺乏导致了界面环境的形成，这解释了ELP凝析液稳定性与界面疏水尺度之间的强相关性，以及蛋白质-水氢键的普遍存在。我们的研究揭示了可能广泛适用的凝析油稳定性和组织的新机制。
The phase separation of intrinsically disordered proteins is emerging as an important mechanism for cellular organization. However, efforts to connect protein sequences to the physical properties of condensates, that is, the molecular grammar, are hampered by a lack of effective approaches for probing high-resolution structural details. Using a combination of multiscale simulations and fluorescence lifetime imaging microscopy experiments, we systematically explored a series of systems consisting of diblock elastin-like polypeptides (ELPs). The simulations succeeded in reproducing the variation of condensate stability upon amino acid substitution and revealed different microenvironments within a single condensate, which we verified with environmentally sensitive fluorophores. The interspersion of hydrophilic and hydrophobic residues and a lack of secondary structure formation result in an interfacial environment, which explains both the strong correlation between ELP condensate stability and interfacial hydrophobicity scales, as well as the prevalence of protein-water hydrogen bonds. Our study uncovers new mechanisms for condensate stability and organization that may be broadly applicable.