De novo engineering of intracellular condensates using artificial disordered proteins

Michael Dzuricky, Bradley A. Rogers, Abdulla Shahid, Paul S. Cremer, Ashutosh Chilkoti

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


Phase separation of intrinsically disordered proteins (IDPs) is a remarkable feature of living cells to dynamically control intracellular partitioning. Despite the numerous new IDPs that have been identified, progress towards rational engineering in cells has been limited. To address this limitation, we systematically scanned the sequence space of native IDPs and designed artificial IDPs (A-IDPs) with different molecular weights and aromatic content, which exhibit variable condensate saturation concentrations and temperature cloud points in vitro and in cells. We created A-IDP puncta using these simple principles, which are capable of sequestering an enzyme and whose catalytic efficiency can be manipulated by the molecular weight of the A-IDP. These results provide a robust engineered platform for creating puncta with new, phase-separation-mediated control of biological function in living cells. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)814-825
Number of pages12
JournalNature Chemistry
Issue number9
StatePublished - Sep 1 2020

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Chemical Engineering


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