Deciphering the link between evolutionarily conserved sequence features and the phase behavior of prion-like low-complexity domains

Abstract

Phase transitions underlie cellular compartmentalization and mediate fundamental biological processes. How they are encoded in the protein sequence is therefore important. Here, we use biophysical experiments, theory, and simulations to generate a conceptual stickers-and-spacers framework to understand phase behavior of intrinsically disordered prion-like low-complexity domains (PLCDs) of RNA-binding proteins. Stickers form non-covalent inter- and intramolecular crosslinks, whereas spacers enable or suppress the formation of these crosslinks.