Saltar al contenido
Merck

Small molecules as potent biphasic modulators of protein liquid-liquid phase separation.

Nature communications (2020-11-06)
W Michael Babinchak, Benjamin K Dumm, Sarah Venus, Solomiia Boyko, Andrea A Putnam, Eckhard Jankowsky, Witold K Surewicz
RESUMEN

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.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Roche
Kit de proliferación celular (MTT)
Sigma-Aldrich
Dextrano from Leuconostoc spp., Mr ~70,000
Sigma-Aldrich
McCoy′s 5A Medium, Modified, with L-glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
poly(A)
Sigma-Aldrich
Sodium benzenesulfonate, 97%
Sigma-Aldrich
Maltose solution, BioReagent, for molecular biology, ~20% in H2O
Sigma-Aldrich
c-di-AMP sodium salt, ≥98% (HPLC)
Sigma-Aldrich
Heparin disaccharide I-H sodium salt
Heparina sodium, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Anti-Mouse IgG1 (γ1), CF488A antibody produced in goat, ~2 mg/mL, affinity isolated antibody, buffered aqueous solution