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A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins

Open access
Wang, Jie, Choi, Jeong-Mo, Holehouse, Alex S., Lee, Hyun O., Zhang, Xiaojie, Jahnel, Marcus, Maharana, Shovamayee, Lemaitre, Régis, Pozniakovsky, Andrei, Drechsel, David, Poser, Ina, Pappu, Rohit V., Alberti, Simon, Hyman, Anthony A.·2018·Cell

Abstract

SUMMARY 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 for phase separation of proteins of the FUS family, and test aspects of this grammar in cells. Phase separation is governed primarily by multivalent interactions amongst 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 sequence.

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Metadata

Authors
Wang, J., Choi, J.-M., Holehouse, A. S., Lee, H. O., Zhang, X., Jahnel, M., Maharana, S., Lemaitre, R., Pozniakovsky, A., Drechsel, D., Poser, I., Pappu, R. V., Alberti, S., & Hyman, A. A.
Venue
Cell
Publisher
Elsevier BV
Published
2018-07
Volume
174
Issue
3
Pages
688-699.e16
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2810866092
Cited by
2,076
References
3
FWCI
52.89
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins. https://app.cochat.ai/papers/10.1016/j.cell.2018.06.006
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Wang, J., Choi, J.-M., Holehouse, A. S., Lee, H. O., Zhang, X., Jahnel, M., Maharana, S., Lemaitre, R., Pozniakovsky, A., Drechsel, D., Poser, I., Pappu, R. V., Alberti, S., & Hyman, A. A. (2018). A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins. Cell. https://doi.org/10.1016/j.cell.2018.06.006

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.