Journal Article Epublish 2 citations
PubMed: 40028898 DOI: 10.7554/eLife.100284
Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates.
Elife 13
Authors: 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
Affiliations
- Department of Biochemistry, University of Toronto, Toronto, Canada.
- Molecular Medicine, Hospital for Sick Children, Toronto, Canada.
- Department 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, Canada.
- Department of Chemistry, Gandhi Institute of Technology and Management, Visakhapatnam, India.
- Department of Molecular Genetics, University of Toronto, Toronto, Canada.
- Department of Chemistry, University of Toronto, Toronto, Canada.
Abstract
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.
MeSH
Biochemistry, Polymers, Biological Science Disciplines, Intrinsically Disordered Proteins
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