Early stages of FUS protein aggregation

The formation of protein droplets through liquid-liquid phase separation is a fundamental process that leads to the formation of membrane organelles such as stress granules and nucleoli. Droplet formation happens through the attachment of single chains sequentially. Fused-in-Sarcoma (FUS) protein has been used as a model to study the aggregation process. The formation of FUS protein droplets is linked to various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). A better understanding of the mechanism underlying FUS droplet formation may provide insight into different biologically essential processes. In this work, we perform computer simulation to elucidate the mechanism of the early stage of FUS protein aggregation using a coarse-grained model of intrinsically disordered protein previously developed by our group. We find that the conformation inside the droplet is heterogeneous and dynamic. The density of the FUS liquid droplet formed in our simulation matches the experimental density.