Journal Article Ppublish 4 citations
PubMed: 39354680 DOI: 10.1093/jmcb/mjae038
ATP promotes protein coacervation through conformational compaction.
J Mol Cell Biol 16(8)
Authors: Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong
Affiliations
- State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China. University of Chinese Academy of Sciences, Beijing 100049, China.
- Zhejiang Province Key Laboratory of Quantum Technology and Device, School of Physics, Zhejiang University, Hangzhou 310058, China.
- College of Chemistry and Molecular Engineering, Beijing National Laboratory for Molecular Sciences & Center for Quantitative Biology, PKU-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
- State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China.
- University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract
Adenosine triphosphate (ATP) has been recognized as a hydrotrope in the phase separation process of intrinsically disordered proteins (IDPs). Surprisingly, when using the disordered Arg-Gly/Arg-Gly-Gly (RG/RGG) rich motif from the HNRNPG protein as a model system, we discover a biphasic relationship between the ATP concentration and IDP phase separation. We show that, at a relatively low ATP concentration, ATP dynamically interacts with the IDP, which neutralizes protein surface charges, promotes intermolecular interactions, and consequently promotes phase separation. We further demonstrate that ATP induces a compact conformation of the IDP, accounting for the reduced solvent exchange rate and lower compression ratio during phase separation. As ATP concentration increases, its hydrotropic properties emerge, leading to the dissolution of the phase-separated droplets. Our finding uncovers a complex mechanism by which ATP molecules modulate the structure, interaction, and phase separation of IDPs and accounts for the distinct phase separation behaviors of the charge-rich RGG motif and other low-complexity IDPs.
MeSH
Molecular Biology, Intrinsically Disordered Proteins