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Updated: Sep 13, 2025
Liquid-cell Transmission Electron Microscopy for Tracking Self-assembly of Nanoparticles
Published on: October 16, 2017
Metal-induced nanoscale clusterization initiates protein liquid-liquid phase separation
Sijia Xiang1, Zhuanghao Hou2, Yu Wang3
1Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230001, China; Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Metal ions like Cu(II) can trigger liquid-liquid phase separation (LLPS) by bridging small ubiquitin-like modifier (SUMO) proteins. This study reveals how metal coordination drives protein condensation and the formation of cellular structures.
Area of Science:
- Biochemistry
- Cell Biology
- Biophysics
Background:
- Liquid-liquid phase separation (LLPS) is vital for cellular function, involving the formation of membrane-less organelles.
- Studying the nucleation seed assembly that triggers LLPS is challenging due to process complexity.
- Metal ions are increasingly recognized for their role in inducing LLPS.
Purpose of the Study:
- To elucidate the assembly mechanism of protein condensation induced by metal ions.
- To investigate the role of copper(II) ions in the phase separation of small ubiquitin-like modifier (SUMO) protein.
- To understand how metal coordination influences protein assembly and LLPS.
Main Methods:
- Utilized small ubiquitin-like modifier (SUMO) protein as a model system.
- Investigated copper(II) (Cu(II)) ion binding sites and their effect on SUMO condensation.
- Employed mass photometry to analyze the dynamic clusterization of SUMO at the nanoscale.
Main Results:
- Identified two weak Cu(II)-binding sites on the SUMO protein surface facilitating intermolecular bridging.
- Confirmed Cu(II)-induced dynamic nanoscale clusterization of SUMO, indicating seed formation.
- Demonstrated that increased Cu(II) binding affinity significantly enhances SUMO protein condensation.
Conclusions:
- Cu(II) coordination plays a pivotal role in driving SUMO protein condensation and subsequent LLPS.
- Non-specific intermolecular metal coordination is a key mechanism in protein assembly.
- This study provides fundamental insights into metal-induced protein condensation and LLPS.
