ATP promotes protein coacervation through conformational compaction  

作　　者：Yueling Zhu Shiyan Lin Lingshen Meng Min Sun Maili Liu Jingyuan Li Chun Tang Zhou Gong 

机构地区：[1]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 [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]Zhejiang Province Key Laboratory of Quantum Technology and Device,School of Physics,Zhejiang University,Hangzhou 310058,China [4]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

出　　处：《Journal of Molecular Cell Biology》2024年第8期46-57,共12页分子细胞生物学报(英文版)

基　　金：supported by grants from the National Natural Science Foundation of China(92353304,31971155,and 21991081);the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2020329).

摘　　要：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.

关 键 词：intrinsically disordered protein phase separation ATP conformational compaction HNRNPG 

分 类 号：O62[理学—有机化学] O641[理学—化学]