Regulating FUS liquid–liquid phase separation via specific metal recognition

文章来源: 发布时间:2023-03-21

Fen Li, Yiyang Lin*, Yan Qiao*

Chinese J. Polym. Sci. 2022, 40, 1043–1049.


Liquid-liquid phase separation (LLPS) or biomolecular condensation that leads to formation of membraneless organelles plays a critical role in many biochemical processes. Mechanical study of regulating LLPS is therefore central to the understanding of protein aggregation and disease-relevant process. We report a Fused in Sarcoma protein (FUS)-derived low complexity (LC) sequence that undergoes LLPS in the presence of metal ions. The LC protein was constructed by fusing a hexhistidine-tag to the N-terminal low complexity domain (the residues 1–165 in QGSY-rich segment) of FUS. Spontaneous condensation of the intrinsic disordered protein into coacervate droplets was observed in the presence of metal ions that chelate oligohistidine moieties to form protein matrix. We demonstrate the key role of metal ion-histidine coordination in governing LLPS behaviours and the fluidity of biomolecular condensates. By taking advantage of competitive binding using chelators, we show the possibility of regulating dynamic behaviours of disease-relevant protein droplets, and developing a potential approach towards controllable biological encapsulate/release.