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

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…

• NS
  National Science Foundation

  Award: MCB1614766
• AF
  American Federation for Aging Research
• SJ
  St. Jude Children's Research Hospital
• AL
  American Lebanese Syrian Associated Charities