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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2023
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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. |
format | Online Article Text |
id | pubmed-9931050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
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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