Tanja Mittag, Member, St. Judy Faculty, Structural Biology Department at St. Jude Children's Research Hospital, will give a talk via Zoom on "Concepts in phase separation – from sequence-encoded driving forces to material properties."

ABSTRACT

Phase transitions underlie cellular compartmentalization and mediate fundamental biological processes. How the driving force for phase separation is encoded in the protein sequence is therefore an important question. 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. We have previously shown that aromatic residues are the stickers in the PLCD of hnRNPA1. Here, we demonstrate that sticker residues mediate networking and spacer residues influence phase separation through their effective solvation volume. Our analytical and coarse-grained models accurately predict PLCD phase behavior. Based on the resulting stickers-and-spacers model, we can think of condensates as network fluids. We are extending our stickers-and-spacers framework to understand material properties of condensates and how their aging processes, which have been linked to neurodegenerative diseases, are influenced by network structure and interfaces.