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

Erik W. Martin, Alex S. Holehouse, Ivan Peran, Mina Farag, J. Jeremias Incicco, Anne Bremer, Christy R. Grace, Andrea Soranno, Rohit V. Pappu, Tanja Mittag

Research output: Contribution to journalArticlepeer-review

209 Scopus citations

Abstract

Prion-like domains (PLDs) can drive liquid-liquid phase separation (LLPS) in cells. Using an integrative biophysical approach that includes nuclear magnetic resonance spectroscopy, small-angle x-ray scattering, and multiscale simulations, we have uncovered sequence features that determine the overall phase behavior of PLDs. We show that the numbers (valence) of aromatic residues in PLDs determine the extent of temperature-dependent compaction of individual molecules in dilute solutions. The valence of aromatic residues also determines full binodals that quantify concentrations of PLDs within coexisting dilute and dense phases as a function of temperature. We also show that uniform patterning of aromatic residues is a sequence feature that promotes LLPS while inhibiting aggregation. Our findings lead to the development of a numerical stickers-and-spacers model that enables predictions of full binodals of PLDs from their sequences.

Original languageEnglish
Pages (from-to)694-699
Number of pages6
JournalScience
Volume367
Issue number6478
DOIs
StatePublished - Feb 7 2020

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