气候变化领域集成服务门户(CCPortal): Ligand effects on phase separation of multivalent macromolecules

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DOI	10.1073/pnas.2017184118
	Ligand effects on phase separation of multivalent macromolecules
	Ruff K.M.; Dar F.; Pappu R.V.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Biomolecular condensates enable spatial and temporal control over cellular processes by concentrating biomolecules into non-stoichiometric assemblies. Many condensates form via reversible phase transitions of condensate-specific multivalent macromolecules known as scaffolds. Phase transitions of scaffolds can be regulated by changing the concentrations of ligands, which are defined as nonscaffold molecules that bind to specific sites on scaffolds. Here, we use theory and computation to uncover rules that underlie ligand-mediated control over scaffold phase behavior. We use the stickers-and-spacers model wherein reversible non-covalent cross-links among stickers drive phase transitions of scaffolds, and spacers modulate the driving forces for phase transitions. We find that the modulatory effects of ligands are governed by the valence of ligands, whether they bind directly to stickers versus spacers, and the relative affinities of ligand–scaffold versus scaffold–scaffold interactions. In general, all ligands have a diluting effect on the concentration of scaffolds within condensates. Whereas monovalent ligands destabilize condensates, multivalent ligands can stabilize condensates by binding directly to spacers or destabilize condensates by binding directly to stickers. Bipartite ligands that bind to stickers and spacers can alter the structural organization of scaffold molecules within condensates even when they have a null effect on condensate stability. Our work highlights the importance of measuring dilute phase concentrations of scaffolds as a function of ligand concentration in cells. This can reveal whether ligands modulate scaffold phase behavior by enabling or suppressing phase separation at endogenous levels, thereby regulating the formation and dissolution of condensates in vivo. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Condensate; Ligand; Polyphasic linkage; Regulation
语种	英语
scopus关键词	article; cell culture; cross linking; in vivo study; macromolecule; phase separation; phase transition
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180377
作者单位	Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States; Center for Science & Engineering of Living Systems, Washington University in St. Louis, St. Louis, MO 63130, United States; Department of Physics, Washington University in St. Louis, St. Louis, MO 63130, United States
推荐引用方式 GB/T 7714	Ruff K.M.,Dar F.,Pappu R.V.. Ligand effects on phase separation of multivalent macromolecules[J],2021,118(10).
APA	Ruff K.M.,Dar F.,&Pappu R.V..(2021).Ligand effects on phase separation of multivalent macromolecules.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Ruff K.M.,et al."Ligand effects on phase separation of multivalent macromolecules".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).