De novo engineering of intracellular condensates using artificial disordered proteins.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Dzuricky, M; Rogers, BA; Shahid, A; Cremer, PS; Chilkoti, A

Published Date

  • September 2020

Published In

Volume / Issue

  • 12 / 9

Start / End Page

  • 814 - 825

PubMed ID

  • 32747754

Pubmed Central ID

  • PMC8281385

Electronic International Standard Serial Number (EISSN)

  • 1755-4349

International Standard Serial Number (ISSN)

  • 1755-4330

Digital Object Identifier (DOI)

  • 10.1038/s41557-020-0511-7

Language

  • eng