Chatterjee Sayantan, Maltseva Daria, Kan Yelena, Hosseini Elnaz, Gonella Grazia, Bonn Mischa, Parekh Sapun H
Department of Biomedical Engineering, University of Texas at Austin, 107 W. Dean Keeton Rd., Austin, TX 78712, USA.
Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz, DE 55128, Germany.
Sci Adv. 2022 Aug 5;8(31):eabm7528. doi: 10.1126/sciadv.abm7528.
Protein condensation into liquid-like structures is critical for cellular compartmentalization, RNA processing, and stress response. Research on protein condensation has primarily focused on membraneless organelles in the absence of lipids. However, the cellular cytoplasm is full of lipid interfaces, yet comparatively little is known about how lipids affect protein condensation. Here, we show that nonspecific interactions between lipids and the disordered fused in sarcoma low-complexity (FUS LC) domain strongly affect protein condensation. In the presence of anionic lipids, FUS LC formed lipid-protein clusters at concentrations more than 30-fold lower than required for pure FUS LC. Lipid-triggered FUS LC clusters showed less dynamic protein organization than canonical, lipid-free FUS LC condensates. Lastly, we found that phosphatidylserine membranes promoted FUS LC condensates having β sheet structures, while phosphatidylglycerol membranes initiated unstructured condensates. Our results show that lipids strongly influence FUS LC condensation, suggesting that protein-lipid interactions modulate condensate formation in cells.
蛋白质凝聚成类液结构对于细胞区室化、RNA加工和应激反应至关重要。蛋白质凝聚的研究主要集中在无脂质情况下的无膜细胞器。然而，细胞质中充满了脂质界面，但关于脂质如何影响蛋白质凝聚却知之甚少。在此，我们表明脂质与无序的肉瘤融合低复杂性（FUS LC）结构域之间的非特异性相互作用强烈影响蛋白质凝聚。在阴离子脂质存在的情况下，FUS LC在浓度比纯FUS LC所需浓度低30多倍时形成脂质-蛋白质簇。脂质触发的FUS LC簇显示出比典型的无脂质FUS LC凝聚物更少的动态蛋白质组织。最后，我们发现磷脂酰丝氨酸膜促进具有β折叠结构的FUS LC凝聚物形成，而磷脂酰甘油膜引发无结构的凝聚物形成。我们的结果表明脂质强烈影响FUS LC凝聚，这表明蛋白质-脂质相互作用调节细胞中的凝聚物形成。
