  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 in general that interchain salt bridges enhance LLPS of
polyelectrolytes such as Caprin1 and that the high valency of ATP-magnesium is
a significant factor for its colocalization with the condensed phases, as
similar trends are observed for several other IDRs. Our findings underscore the
role of biomolecular condensates in modulating ion concentrations and its
functional ramifications.
