Journal
CELL
Volume 174, Issue 3, Pages 688-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2018.06.006
Keywords
-
Categories
Funding
- Max Planck Society
- MaxSynBio Consortium
- U.S. NIH [5R01NS056114]
- Research Collaborative on Membraneless Organelles from the St. Jude Children's Research Hospital
- ERC [725836, 643417]
- BMBF [01ED1601A, 031A359A]
- JPND (CureALS)
- Human Frontier Science Program [RGP0034/2017]
- European Research Council (ERC) [725836] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
Proteins such as FUS phase separate to form liquid-like condensates that can harden into less dynamic structures. However, how these properties emerge from the collective interactions of many amino acids remains largely unknown. Here, we use extensive mutagenesis to identify a sequence-encoded molecular grammar underlying the driving forces of phase separation of proteins in the FUS family and test aspects of this grammar in cells. Phase separation is primarily governed by multivalent interactions among tyrosine residues from prion-like domains and arginine residues from RNA-binding domains, which are modulated by negatively charged residues. Glycine residues enhance the fluidity, whereas glutamine and serine residues promote hardening. We develop a model to show that the measured saturation concentrations of phase separation are inversely proportional to the product of the numbers of arginine and tyrosine residues. These results suggest it is possible to predict phase-separation properties based on amino acid sequences.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available