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DOI	10.1073/pnas.2104897118
	Interaction hot spots for phase separation revealed by NMR studies of a CAPRIN1 condensed phase
	Kim T.H.; Payliss B.J.; Nosella M.L.; Lee I.T.W.; Toyama Y.; Forman-Kay J.D.; Kay L.E.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:23
英文摘要	The role of biomolecular condensates in regulating biological function and the importance of dynamic interactions involving intrinsically disordered protein regions (IDRs) in their assembly are increasingly appreciated. While computational and theoretical approaches have provided significant insights into IDR phase behavior, establishing the critical interactions that govern condensation with atomic resolution through experiment is more difficult, given the lack of applicability of standard structural biological tools to study these highly dynamic large-scale associated states. NMR can be a valuable method, but the dynamic and viscous nature of condensed IDRs presents challenges. Using the C-terminal IDR (607 to 709) of CAPRIN1, an RNA-binding protein found in stress granules, P bodies, and messenger RNA transport granules, we have developed and applied a variety of NMR methods for studies of condensed IDR states to provide insights into interactions driving and modulating phase separation. We identify ATP interactions with CAPRIN1 that can enhance or reduce phase separation. We also quantify specific side-chain and backbone interactions within condensed CAPRIN1 that define critical sequences for phase separation and that are reduced by O-GlcNAcylation known to occur during cell cycle and stress. This expanded NMR toolkit that has been developed for characterizing IDR condensates has generated detailed interaction information relevant for understanding CAPRIN1 biology and informing general models of phase separation, with significant potential future applications to illuminate dynamic structure-function relationships in other biological condensates. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Biomolecular condensates; Intrinsically disordered protein regions; Modification of phase separation by ATP and O-GlcNAcylation; NMR methods for studying condensates; Site-specific intermolecular interactions
语种	英语
scopus关键词	caprin1 protein; intrinsically disordered protein; RNA binding protein; unclassified drug; acylation; Article; carboxy terminal sequence; computer model; controlled study; Escherichia coli; nonhuman; nuclear magnetic resonance; phase separation; priority journal; protein protein interaction; RNA transport
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/238897
作者单位	Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Program in Molecular Medicine, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
推荐引用方式 GB/T 7714	Kim T.H.,Payliss B.J.,Nosella M.L.,et al. Interaction hot spots for phase separation revealed by NMR studies of a CAPRIN1 condensed phase[J],2021,118(23).
APA	Kim T.H..,Payliss B.J..,Nosella M.L..,Lee I.T.W..,Toyama Y..,...&Kay L.E..(2021).Interaction hot spots for phase separation revealed by NMR studies of a CAPRIN1 condensed phase.Proceedings of the National Academy of Sciences of the United States of America,118(23).
MLA	Kim T.H.,et al."Interaction hot spots for phase separation revealed by NMR studies of a CAPRIN1 condensed phase".Proceedings of the National Academy of Sciences of the United States of America 118.23(2021).