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arXiv · 2401.04873

Electrostatics of Salt-Dependent Reentrant Phase Behaviors Highlights Diverse Roles of ATP in Biomolecular Condensates

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
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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, e.g., 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 $\pi$-related interactions and as an amphiphilic hydrotrope, underscoring a general role of biomolecular condensates in modulating ion concentrations and its functional ramifications.

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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. 2024-01-10. Electrostatics of Salt-Dependent Reentrant Phase Behaviors Highlights Diverse Roles of ATP in Biomolecular Condensates. https://doi.org/10.7554/elife.100284

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