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Regulating FUS Liquid-Liquid Phase Separation via Specific Metal Recognition

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Abstract

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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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 22072159 and 22172007), the Fundamental Research Funds for the Central Universities (No. buctrc202015).

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Authors and Affiliations

  1. 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

    Fen Li & Yan Qiao

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Fen Li & Yan Qiao

  3. State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China

    Yiyang Lin

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  1. Fen Li
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Correspondence to Yiyang Lin or Yan Qiao.

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Li, F., Lin, Y. & Qiao, Y. Regulating FUS Liquid-Liquid Phase Separation via Specific Metal Recognition. Chin J Polym Sci 40, 1043–1049 (2022). https://doi.org/10.1007/s10118-022-2763-8

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