James Shorter

Bede Portz, Bo Lim Lee, James Shorter

Trends in Biochemical Sciences: https://doi.org/10.1016/j.tibs.2020.12.005

Phase separation by proteins containing intrinsically-disordered regions (IDRs) underpins the biogenesis of functional membraneless organelles, as well as the formation of aggregated structures linked to neurodegenerative disease.

One class of IDR, termed a prion-like domain (PrLD), is frequently found in RNA-binding proteins, such as FUS and TDP-43, which form condensates with a range of material states.

FUS and TDP-43 form condensates in health and disease, and their phase separation is governed by distinct molecular grammar and regulation.

Aberrant phase separation is likely more diverse than liquid-to-solid transitions and may include inappropriate liquid phases.

Drugging condensates to treat disease is a promising strategy that may involve altering saturation concentrations of key scaffolds, or the specific partitioning of disruptive agents into discrete condensates.