Open AccessDe novo engineering of intracellular condensates using artificial disordered proteins
Author(s) -
Michael Dzuricky,
Bradley A. Rogers,
Abdulla Shahid,
Paul S. Cremer,
Ashutosh Chilkoti
Publication year - 2020
Publication title -
nature chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.996
H-Index - 232
eISSN - 1755-4349
pISSN - 1755-4330
DOI - 10.1038/s41557-020-0511-7
Subject(s) - chemistry , intrinsically disordered proteins , intracellular , rational design , phase (matter) , biophysics , nanotechnology , computational biology , biochemistry , biology , organic chemistry , materials science
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.