Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation

Abstract Recently many cellular functions have been associated with membraneless organelles, or protein droplets, formed by liquid-liquid phase separation (LLPS). Proteins in these droplets often contain RNA-binding domains, but the effects of RNA on LLPS have been controversial. To gain better unde...

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Autores principales:	Valery Nguemaha, Huan-Xiang Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5221a37cab9a4f7d9cb8e43032e5b64e
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spelling	oai:doaj.org-article:5221a37cab9a4f7d9cb8e43032e5b64e2021-12-02T16:08:26ZLiquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation10.1038/s41598-018-25132-12045-2322https://doaj.org/article/5221a37cab9a4f7d9cb8e43032e5b64e2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25132-1https://doaj.org/toc/2045-2322Abstract Recently many cellular functions have been associated with membraneless organelles, or protein droplets, formed by liquid-liquid phase separation (LLPS). Proteins in these droplets often contain RNA-binding domains, but the effects of RNA on LLPS have been controversial. To gain better understanding on the roles of RNA and other macromolecular regulators, here we used Gibbs-ensemble simulations to determine phase diagrams of two-component patchy particles, as models for mixtures of proteins with regulatory components. Protein-like particles have four patches, with attraction strength ε PP; regulatory particles experience mutual steric repulsion but have two attractive patches toward proteins, with the strength ε PR tunable. At low ε PR, the regulator, due to steric repulsion, preferentially partitions in the dispersed phase, thereby displacing the protein into the droplet phase and promoting LLPS. At moderate ε PR, the regulator starts to partition and displace the protein in the droplet phase, but only to weaken bonding networks and thereby suppress LLPS. At ε PR > ε PP, the enhanced bonding ability of the regulator initially promotes LLPS, but at higher amounts, the resulting displacement of the protein suppresses LLPS. These results illustrate how RNA can have disparate effects on LLPS, thus able to perform diverse functions in different organelles.Valery NguemahaHuan-Xiang ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Valery Nguemaha Huan-Xiang Zhou Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation
description	Abstract Recently many cellular functions have been associated with membraneless organelles, or protein droplets, formed by liquid-liquid phase separation (LLPS). Proteins in these droplets often contain RNA-binding domains, but the effects of RNA on LLPS have been controversial. To gain better understanding on the roles of RNA and other macromolecular regulators, here we used Gibbs-ensemble simulations to determine phase diagrams of two-component patchy particles, as models for mixtures of proteins with regulatory components. Protein-like particles have four patches, with attraction strength ε PP; regulatory particles experience mutual steric repulsion but have two attractive patches toward proteins, with the strength ε PR tunable. At low ε PR, the regulator, due to steric repulsion, preferentially partitions in the dispersed phase, thereby displacing the protein into the droplet phase and promoting LLPS. At moderate ε PR, the regulator starts to partition and displace the protein in the droplet phase, but only to weaken bonding networks and thereby suppress LLPS. At ε PR > ε PP, the enhanced bonding ability of the regulator initially promotes LLPS, but at higher amounts, the resulting displacement of the protein suppresses LLPS. These results illustrate how RNA can have disparate effects on LLPS, thus able to perform diverse functions in different organelles.
format	article
author	Valery Nguemaha Huan-Xiang Zhou
author_facet	Valery Nguemaha Huan-Xiang Zhou
author_sort	Valery Nguemaha
title	Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation
title_short	Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation
title_full	Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation
title_fullStr	Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation
title_full_unstemmed	Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation
title_sort	liquid-liquid phase separation of patchy particles illuminates diverse effects of regulatory components on protein droplet formation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/5221a37cab9a4f7d9cb8e43032e5b64e
work_keys_str_mv	AT valerynguemaha liquidliquidphaseseparationofpatchyparticlesilluminatesdiverseeffectsofregulatorycomponentsonproteindropletformation AT huanxiangzhou liquidliquidphaseseparationofpatchyparticlesilluminatesdiverseeffectsofregulatorycomponentsonproteindropletformation
_version_	1718384467550142464

Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation

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