Protein Folding in Coacervates

Intrinsically disordered proteins are ubiquitous in biology. Some play roles in the formation of membraneless organelles through coacervation; others fold upon binding to certain molecular partners. In living cells, membraneless organelles sequester a whole range of proteins and other biomolecules. We propose to investigate how the sequestration of proteins by coacervates, such as in membraneless organelles, affects protein folding. We hypothesize that especially the folding of intrinsically disordered proteins that fold upon binding to molecular partners, could be sensitive to sequestration by coacervates. This hypothesis is motivated by puzzling observations we have made on the folding of the intrinsically disordered bacterial protein lanmodulin (whose folding is induced by the binding of rare earth metal ions) in coacervate droplets consisting of elastin-like polypeptides. This is also the model system that we will use to investigate the fundamental biophysical phenomenon of how coacervate environments can affect protein folding. The observed results will help us better understand how liquid-liquid phase separation plays a role in biology and could translate into the use of coacervates for various applications.