In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins
Intrinsically disordered proteins (IDPs) are essential players in the assembly of biomolecular condensates during liquid–liquid phase separation (LLPS). Disordered regions (IDRs) are significantly exposed to the solvent and, therefore, highly influenced by fluctuations in the microenvironment. Extri...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/7/974 |
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| author | Carlos Pintado-Grima Oriol Bárcenas Salvador Ventura |
| author_facet | Carlos Pintado-Grima Oriol Bárcenas Salvador Ventura |
| author_sort | Carlos Pintado-Grima |
| collection | DOAJ |
| description | Intrinsically disordered proteins (IDPs) are essential players in the assembly of biomolecular condensates during liquid–liquid phase separation (LLPS). Disordered regions (IDRs) are significantly exposed to the solvent and, therefore, highly influenced by fluctuations in the microenvironment. Extrinsic factors, such as pH, modify the solubility and disorder state of IDPs, which in turn may impact the formation of liquid condensates. However, little attention has been paid to how the solution pH influences LLPS, despite knowing that this process is context-dependent. Here, we have conducted a large-scale in-silico analysis of pH-dependent solubility and disorder in IDRs known to be involved in LLPS (LLPS-DRs). We found that LLPS-DRs present maximum solubility around physiological pH, where LLPS often occurs, and identified significant differences in solubility and disorder between proteins that can phase-separate by themselves or those that require a partner. We also analyzed the effect of mutations in the resulting solubility profiles of LLPS-DRs and discussed how, as a general trend, LLPS-DRs display physicochemical properties that permit their LLPS at physiologically relevant pHs. |
| first_indexed | 2024-03-09T03:39:34Z |
| format | Article |
| id | doaj.art-88ae7e0d42044155b1070917ca621dea |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T03:39:34Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-88ae7e0d42044155b1070917ca621dea2023-12-03T14:43:42ZengMDPI AGBiomolecules2218-273X2022-07-0112797410.3390/biom12070974In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered ProteinsCarlos Pintado-Grima0Oriol Bárcenas1Salvador Ventura2Institut de Biotecnologia i Biomedicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, SpainInstitut de Biotecnologia i Biomedicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, SpainInstitut de Biotecnologia i Biomedicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, SpainIntrinsically disordered proteins (IDPs) are essential players in the assembly of biomolecular condensates during liquid–liquid phase separation (LLPS). Disordered regions (IDRs) are significantly exposed to the solvent and, therefore, highly influenced by fluctuations in the microenvironment. Extrinsic factors, such as pH, modify the solubility and disorder state of IDPs, which in turn may impact the formation of liquid condensates. However, little attention has been paid to how the solution pH influences LLPS, despite knowing that this process is context-dependent. Here, we have conducted a large-scale in-silico analysis of pH-dependent solubility and disorder in IDRs known to be involved in LLPS (LLPS-DRs). We found that LLPS-DRs present maximum solubility around physiological pH, where LLPS often occurs, and identified significant differences in solubility and disorder between proteins that can phase-separate by themselves or those that require a partner. We also analyzed the effect of mutations in the resulting solubility profiles of LLPS-DRs and discussed how, as a general trend, LLPS-DRs display physicochemical properties that permit their LLPS at physiologically relevant pHs.https://www.mdpi.com/2218-273X/12/7/974pHliquid-liquid phase separationintrinsically disordered proteinsprotein solubilityprotein disordermutations |
| spellingShingle | Carlos Pintado-Grima Oriol Bárcenas Salvador Ventura In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins Biomolecules pH liquid-liquid phase separation intrinsically disordered proteins protein solubility protein disorder mutations |
| title | In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins |
| title_full | In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins |
| title_fullStr | In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins |
| title_full_unstemmed | In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins |
| title_short | In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins |
| title_sort | in silico analysis of ph dependent liquid liquid phase separation in intrinsically disordered proteins |
| topic | pH liquid-liquid phase separation intrinsically disordered proteins protein solubility protein disorder mutations |
| url | https://www.mdpi.com/2218-273X/12/7/974 |
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