a.Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory of Polymer Physics and Chemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
b.University of Chinese Academy of Sciences, Beijing 100049, China
c.State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
y.lin@mail.buct.edu.cn (Y.L.)
yanqiao@iccas.ac.cn (Y.Q.)
收稿:2022-03-16,
修回:2022-04-12,
录用:2022-04-15,
网络首发:2022-06-24,
纸质出版:2022-09-01
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Li, F.; Lin, Y.; Qiao, Y. Regulating FUS liquid-liquid phase separation via specific metal recognition. Chinese J. Polym. Sci. 2022, 40, 1043–1049
Fen Li, Yiyang Lin, Yan Qiao. Regulating FUS Liquid-Liquid Phase Separation
Li, F.; Lin, Y.; Qiao, Y. Regulating FUS liquid-liquid phase separation via specific metal recognition. Chinese J. Polym. Sci. 2022, 40, 1043–1049 DOI: 10.1007/s10118-022-2763-8.
Fen Li, Yiyang Lin, Yan Qiao. Regulating FUS Liquid-Liquid Phase Separation
We design a fused in sarcoma (FUS)-derived protein by fusing a hexhistidine-tag to the low complexity domain of FUS
which undergoes liquid-liquid phase separation in the presence of metal ions. Regulation of dynamic coacervation of FUS with the competitive binding strategy offers a possibility to design protocells as a controlled release system.
Liquid-liquid phase separation (LLPS) or biomolecular condensation that leads to formation of membraneless organelles plays a critical role in many biochemical processes. Mechanism 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 behaviors of disease-relevant protein droplets
and developing a potential approach towards controllable biological encapsulation/release.
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