Abstract
Fused in Sarcoma (FUS) is an essential RNA-processing protein functioning via self-assembly including through Liquid-Liquid Phase Separation (LLPS) and implicated in amyotrophic lateral sclerosis and frontotemporal dementia pathologies through aberrant subsequent neurodegeneration. However, the biomolecular interactions driving LLPS have not been thoroughly characterized. In this work, we probe in detail the role of each of the enriched residues types in FUS in LLPS. We present a number of mutagenic and biochemical-derived systems that refine our understanding of the roles of individual amino acid types beyond tyrosine and arginine in FUS phase separation.
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