Determinants that enable disordered protein assembly into discrete condensed phases. Academic Article uri icon


  • Cells harbour numerous mesoscale membraneless compartments that house specific biochemical processes and perform distinct cellular functions. These protein- and RNA-rich bodies are thought to form through multivalent interactions among proteins and nucleic acids, resulting in demixing via liquid-liquid phase separation. Proteins harbouring intrinsically disordered regions (IDRs) predominate in membraneless organelles. However, it is not known whether IDR sequence alone can dictate the formation of distinct condensed phases. We identified a pair of IDRs capable of forming spatially distinct condensates when expressed in cells. When reconstituted in vitro, these model proteins do not co-partition, suggesting condensation specificity is encoded directly in the polypeptide sequences. Through computational modelling and mutagenesis, we identified the amino acids and chain properties governing homotypic and heterotypic interactions that direct selective condensation. These results form the basis of physicochemical principles that may direct subcellular organization of IDRs into specific condensates and reveal an IDR code that can guide construction of orthogonal membraneless compartments.

published proceedings

  • Nat Chem

altmetric score

  • 48.6

author list (cited authors)

  • Welles, R. M., Sojitra, K. A., Garabedian, M. V., Xia, B., Wang, W., Guan, M., ... Good, M. C.

citation count

  • 3

complete list of authors

  • Welles, Rachel M||Sojitra, Kandarp A||Garabedian, Mikael V||Xia, Boao||Wang, Wentao||Guan, Muyang||Regy, Roshan M||Gallagher, Elizabeth R||Hammer, Daniel A||Mittal, Jeetain||Good, Matthew C

publication date

  • February 2024