Valence and patterning of aromatic residues determine the phase behavior of prion-like domains

TLDR

Liquid‑liquid phase separation is increasingly recognized in cellular processes, and prion‑like domains—rich in polar amino acids and aromatic residues—have been implicated in this phenomenon. The authors quantified PLD concentrations in dilute and dense phases across temperatures, showing that aromatic residue number and patterning govern LLPS, and they introduced a sticker‑and‑spacers model to predict phase behavior from sequence. They found that increasing aromatic residue count and uniform patterning enhances LLPS while suppressing aggregation. Science, this issue p.

Abstract

Not too sticky There is increasing evidence for a role of liquid-liquid phase separation (LLPS) in many cellular processes. Many proteins that undergo LLPS include prionlike domains (PLDs), which are enriched in polar amino acids and often interspersed with aromatic residues. Combining experimental data with simulations, Martin et al. quantified concentrations of PLDs in coexisting dilute and dense phases as a function of temperature and show that the phase behavior is determined by the number of aromatic residues and their patterning, with uniform patterning of aromatic residues promoting LLPS and inhibiting aggregation. They developed a sticker-and-spacers model that can predict the phase behavior of PLDs on the basis of their sequence. Science , this issue p. 694