期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-020-19211-z
关键词
-
资金
- NIH [F30 AG059350, R01 NS103848, RF1 AG061797, R35 GM118088, T32 NS077888, T32 GM007250]
- Paul Berg and Harland Wood Graduate Fellowship
- NIH ORIP grants [S10 OD024996, S10 RR021228]
Liquid-liquid phase separation (LLPS) of proteins that leads to formation of membrane-less organelles is critical to many biochemical processes in the cell. However, dysregulated LLPS can also facilitate aberrant phase transitions and lead to protein aggregation and disease. Accordingly, there is great interest in identifying small molecules that modulate LLPS. Here, we demonstrate that 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) and similar compounds are potent biphasic modulators of protein LLPS. Depending on context, bis-ANS can both induce LLPS de novo as well as prevent formation of homotypic liquid droplets. Our study also reveals the mechanisms by which bis-ANS and related compounds modulate LLPS and identify key chemical features of small molecules required for this activity. These findings may provide a foundation for the rational design of small molecule modulators of LLPS with therapeutic value. Dysregulated liquid-liquid phase separation (LLPS) of proteins can facilitate aberrant phase transitions and lead to protein aggregation and disease. Here, authors demonstrate that 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) and similar compounds are potent biphasic modulators of protein LLPS.
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