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Thermodynamic origins of two-component multiphase condensates of proteins

Intracellular condensates are highly multi-component systems in which complex phase behaviour can ensue, including the formation of architectures comprising multiple immiscible condensed phases. Relying solely on physical intuition to manipulate such condensates is difficult because of the complexit...

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Autores principales: Chew, Pin Yu, Joseph, Jerelle A., Collepardo-Guevara, Rosana, Reinhardt, Aleks
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931050/
https://www.ncbi.nlm.nih.gov/pubmed/36819870
http://dx.doi.org/10.1039/d2sc05873a
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author Chew, Pin Yu
Joseph, Jerelle A.
Collepardo-Guevara, Rosana
Reinhardt, Aleks
author_facet Chew, Pin Yu
Joseph, Jerelle A.
Collepardo-Guevara, Rosana
Reinhardt, Aleks
author_sort Chew, Pin Yu
collection PubMed
description Intracellular condensates are highly multi-component systems in which complex phase behaviour can ensue, including the formation of architectures comprising multiple immiscible condensed phases. Relying solely on physical intuition to manipulate such condensates is difficult because of the complexity of their composition, and systematically learning the underlying rules experimentally would be extremely costly. We address this challenge by developing a computational approach to design pairs of protein sequences that result in well-separated multilayered condensates and elucidate the molecular origins of these compartments. Our method couples a genetic algorithm to a residue-resolution coarse-grained protein model. We demonstrate that we can design protein partners to form multiphase condensates containing naturally occurring proteins, such as the low-complexity domain of hnRNPA1 and its mutants, and show how homo- and heterotypic interactions must differ between proteins to result in multiphasicity. We also show that in some cases the specific pattern of amino-acid residues plays an important role. Our findings have wide-ranging implications for understanding and controlling the organisation, functions and material properties of biomolecular condensates.
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spelling pubmed-99310502023-02-16 Thermodynamic origins of two-component multiphase condensates of proteins Chew, Pin Yu Joseph, Jerelle A. Collepardo-Guevara, Rosana Reinhardt, Aleks Chem Sci Chemistry Intracellular condensates are highly multi-component systems in which complex phase behaviour can ensue, including the formation of architectures comprising multiple immiscible condensed phases. Relying solely on physical intuition to manipulate such condensates is difficult because of the complexity of their composition, and systematically learning the underlying rules experimentally would be extremely costly. We address this challenge by developing a computational approach to design pairs of protein sequences that result in well-separated multilayered condensates and elucidate the molecular origins of these compartments. Our method couples a genetic algorithm to a residue-resolution coarse-grained protein model. We demonstrate that we can design protein partners to form multiphase condensates containing naturally occurring proteins, such as the low-complexity domain of hnRNPA1 and its mutants, and show how homo- and heterotypic interactions must differ between proteins to result in multiphasicity. We also show that in some cases the specific pattern of amino-acid residues plays an important role. Our findings have wide-ranging implications for understanding and controlling the organisation, functions and material properties of biomolecular condensates. The Royal Society of Chemistry 2023-01-25 /pmc/articles/PMC9931050/ /pubmed/36819870 http://dx.doi.org/10.1039/d2sc05873a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Chew, Pin Yu
Joseph, Jerelle A.
Collepardo-Guevara, Rosana
Reinhardt, Aleks
Thermodynamic origins of two-component multiphase condensates of proteins
title Thermodynamic origins of two-component multiphase condensates of proteins
title_full Thermodynamic origins of two-component multiphase condensates of proteins
title_fullStr Thermodynamic origins of two-component multiphase condensates of proteins
title_full_unstemmed Thermodynamic origins of two-component multiphase condensates of proteins
title_short Thermodynamic origins of two-component multiphase condensates of proteins
title_sort thermodynamic origins of two-component multiphase condensates of proteins
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931050/
https://www.ncbi.nlm.nih.gov/pubmed/36819870
http://dx.doi.org/10.1039/d2sc05873a
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