Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates
Liquid-liquid phase separation (LLPS) involving intrinsically disordered protein regions (IDRs) is a major physical mechanism for biological membraneless compartmentalization. The multifaceted electrostatic effects in these biomolecular condensates are exemplified here by experimental and theoretica...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-03-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/100284 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850240484013768704 |
|---|---|
| author | Yi-Hsuan Lin Tae Hun Kim Suman Das Tanmoy Pal Jonas Wessén Atul Kaushik Rangadurai Lewis E Kay Julie D Forman-Kay Hue Sun Chan |
| author_facet | Yi-Hsuan Lin Tae Hun Kim Suman Das Tanmoy Pal Jonas Wessén Atul Kaushik Rangadurai Lewis E Kay Julie D Forman-Kay Hue Sun Chan |
| author_sort | Yi-Hsuan Lin |
| collection | DOAJ |
| description | Liquid-liquid phase separation (LLPS) involving intrinsically disordered protein regions (IDRs) is a major physical mechanism for biological membraneless compartmentalization. The multifaceted electrostatic effects in these biomolecular condensates are exemplified here by experimental and theoretical investigations of the different salt- and ATP-dependent LLPSs of an IDR of messenger RNA-regulating protein Caprin1 and its phosphorylated variant pY-Caprin1, exhibiting, for example, reentrant behaviors in some instances but not others. Experimental data are rationalized by physical modeling using analytical theory, molecular dynamics, and polymer field-theoretic simulations, indicating that interchain ion bridges enhance LLPS of polyelectrolytes such as Caprin1 and the high valency of ATP-magnesium is a significant factor for its colocalization with the condensed phases, as similar trends are observed for other IDRs. The electrostatic nature of these features complements ATP’s involvement in π-related interactions and as an amphiphilic hydrotrope, underscoring a general role of biomolecular condensates in modulating ion concentrations and its functional ramifications. |
| format | Article |
| id | doaj-art-4a6c258cd3384322b50954bcfb19ea5b |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-4a6c258cd3384322b50954bcfb19ea5b2025-08-20T02:00:51ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011310.7554/eLife.100284Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensatesYi-Hsuan Lin0Tae Hun Kim1Suman Das2Tanmoy Pal3Jonas Wessén4https://orcid.org/0000-0002-5904-8442Atul Kaushik Rangadurai5Lewis E Kay6https://orcid.org/0000-0002-4054-4083Julie D Forman-Kay7https://orcid.org/0000-0001-8265-972XHue Sun Chan8https://orcid.org/0000-0002-1381-923XDepartment of Biochemistry, University of Toronto, Toronto, Canada; Molecular Medicine, Hospital for Sick Children, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, Canada; Molecular Medicine, Hospital for Sick Children, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada; Department of Chemistry, University of Toronto, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, Canada; Department of Chemistry, Gandhi Institute of Technology and Management, Visakhapatnam, IndiaDepartment of Biochemistry, University of Toronto, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, Canada; Molecular Medicine, Hospital for Sick Children, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada; Department of Chemistry, University of Toronto, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, Canada; Molecular Medicine, Hospital for Sick Children, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada; Department of Chemistry, University of Toronto, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, Canada; Molecular Medicine, Hospital for Sick Children, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, CanadaLiquid-liquid phase separation (LLPS) involving intrinsically disordered protein regions (IDRs) is a major physical mechanism for biological membraneless compartmentalization. The multifaceted electrostatic effects in these biomolecular condensates are exemplified here by experimental and theoretical investigations of the different salt- and ATP-dependent LLPSs of an IDR of messenger RNA-regulating protein Caprin1 and its phosphorylated variant pY-Caprin1, exhibiting, for example, reentrant behaviors in some instances but not others. Experimental data are rationalized by physical modeling using analytical theory, molecular dynamics, and polymer field-theoretic simulations, indicating that interchain ion bridges enhance LLPS of polyelectrolytes such as Caprin1 and the high valency of ATP-magnesium is a significant factor for its colocalization with the condensed phases, as similar trends are observed for other IDRs. The electrostatic nature of these features complements ATP’s involvement in π-related interactions and as an amphiphilic hydrotrope, underscoring a general role of biomolecular condensates in modulating ion concentrations and its functional ramifications.https://elifesciences.org/articles/100284liquid-liquid phase separationphosphorylationintrinsically disordered proteinsrandom phase approximationfield-theoretic simulationmolecular dynamics |
| spellingShingle | Yi-Hsuan Lin Tae Hun Kim Suman Das Tanmoy Pal Jonas Wessén Atul Kaushik Rangadurai Lewis E Kay Julie D Forman-Kay Hue Sun Chan Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates eLife liquid-liquid phase separation phosphorylation intrinsically disordered proteins random phase approximation field-theoretic simulation molecular dynamics |
| title | Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates |
| title_full | Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates |
| title_fullStr | Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates |
| title_full_unstemmed | Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates |
| title_short | Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates |
| title_sort | electrostatics of salt dependent reentrant phase behaviors highlights diverse roles of atp in biomolecular condensates |
| topic | liquid-liquid phase separation phosphorylation intrinsically disordered proteins random phase approximation field-theoretic simulation molecular dynamics |
| url | https://elifesciences.org/articles/100284 |
| work_keys_str_mv | AT yihsuanlin electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates AT taehunkim electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates AT sumandas electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates AT tanmoypal electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates AT jonaswessen electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates AT atulkaushikrangadurai electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates AT lewisekay electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates AT juliedformankay electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates AT huesunchan electrostaticsofsaltdependentreentrantphasebehaviorshighlightsdiverserolesofatpinbiomolecularcondensates |