globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1907849116
论文题名:
Three archetypical classes of macromolecular regulators of protein liquid-liquid phase separation
作者: Ghosh A.; Mazarakos K.; Zhou H.-X.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2019
卷: 116, 期:39
起始页码: 19474
结束页码: 19483
语种: 英语
英文关键词: Liquid-liquid phase separation ; Macromolecular regulator ; Membraneless organelles ; Partition coefficient
Scopus关键词: heparin ; lysozyme ; proline ; protein ; Article ; cell organelle ; concentration (parameter) ; controlled study ; liquid liquid phase separation ; macromolecule ; membraneless organelle ; nonhuman ; partition coefficient ; phase separation ; prediction ; priority journal ; protein domain ; protein motif ; volume
英文摘要: Membraneless organelles, corresponding to the droplet phase upon liquid-liquid phase separation (LLPS) of protein or protein- RNA mixtures, mediate myriad cellular functions. Cells use a variety of biochemical signals such as expression level and posttranslational modification to regulate droplet formation and dissolution, but the physical basis of the regulatory mechanisms remains illdefined and quantitative assessment of the effects is largely lacking. Our computational study predicted that the strength of attraction by droplet-forming proteins dictates whether and how macromolecular regulators promote or suppress LLPS. We experimentally tested this prediction, using the pentamers of SH3 domains and proline-rich motifs (SH35 and PRM5) as droplet-forming proteins. Determination of the changes in phase boundary and the partition coefficients in the droplet phase over a wide range of regulator concentrations yielded both a quantitative measure and a mechanistic understanding of the regulatory effects. Three archetypical classes of regulatory effects were observed. Ficoll 70 at high concentrations indirectly promoted SH35-PRM5 LLPS, by taking up volume in the bulk phase and thereby displacing SH35 and PRM5 into the droplet phase. Lysozyme had a moderate partition coefficient and suppressed LLPS by substituting weaker attraction with SH35 for the stronger SH35-PRM5 attraction in the droplet phase. By forming even stronger attraction with PRM5, heparin at low concentrations partitioned heavily into the droplet phase and promoted LLPS. These characteristics were recapitulated by computational results of patchy particle models, validating the identification of the 3 classes of macromolecular regulators as volume-exclusion promotors, weak-attraction suppressors, and strong-attraction promotors. © 2019 National Academy of Sciences. All rights reserved.
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163530
Appears in Collections:气候变化与战略

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作者单位: Ghosh, A., Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, United States, Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, United States, Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, United States; Mazarakos, K., Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, United States, Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, United States; Zhou, H.-X., Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, United States, Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, United States

Recommended Citation:
Ghosh A.,Mazarakos K.,Zhou H.-X.. Three archetypical classes of macromolecular regulators of protein liquid-liquid phase separation[J]. Proceedings of the National Academy of Sciences of the United States of America,2019-01-01,116(39)
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