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DOI10.1073/PNAS.2007670117
Widespread occurrence of the droplet state of proteins in the human proteome
Hardenberg M.; Horvath A.; Ambrus V.; Fuxreiter M.; Vendruscolo M.
发表日期2021
ISSN00278424
起始页码33254
结束页码33262
卷号117期号:52
英文摘要A wide range of proteins have been reported to condensate into a dense liquid phase, forming a reversible droplet state. Failure in the control of the droplet state can lead to the formation of the more stable amyloid state, which is often disease-related. These observations prompt the question of how many proteins can undergo liquid–liquid phase separation. Here, in order to address this problem, we discuss the biophysical principles underlying the droplet state of proteins by analyzing current evidence for droplet-driver and droplet-client proteins. Based on the concept that the droplet state is stabilized by the large conformational entropy associated with nonspecific side-chain interactions, we develop the FuzDrop method to predict droplet-promoting regions and proteins, which can spontaneously phase separate. We use this approach to carry out a proteome-level study to rank proteins according to their propensity to form the droplet state, spontaneously or via partner interactions. Our results lead to the conclusion that the droplet state could be, at least transiently, accessible to most proteins under conditions found in the cellular environment. © 2020 National Academy of Sciences. All rights reserved.
英文关键词Liquid–liquid phase separation; Protein condensates; Protein droplets
语种英语
scopus关键词alpha synuclein; amino acid; beta synuclein; protein; protein binding; proteome; animal; chemistry; entropy; human; liquid liquid extraction; metabolism; protein conformation; reproducibility; alpha-Synuclein; Amino Acids; Animals; beta-Synuclein; Entropy; Humans; Liquid-Liquid Extraction; Protein Binding; Protein Conformation; Proteins; Proteome; Reproducibility of Results
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/179688
作者单位Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom; John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia; Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, H-4010, Hungary; Department of Biomedical Sciences, University of Padova, Padova, 35131, Italy
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Hardenberg M.,Horvath A.,Ambrus V.,et al. Widespread occurrence of the droplet state of proteins in the human proteome[J],2021,117(52).
APA Hardenberg M.,Horvath A.,Ambrus V.,Fuxreiter M.,&Vendruscolo M..(2021).Widespread occurrence of the droplet state of proteins in the human proteome.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA Hardenberg M.,et al."Widespread occurrence of the droplet state of proteins in the human proteome".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).
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