The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins
Open accessAbstract
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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Kato, M., Han, T. W., Xie, S., Shi, K., Du, X., Wu, L. C., Mirzaei, H., Goldsmith, E. J., Longgood, J., Pei, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.017 · Cited by 2,012
A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances
Hein, M. Y., Hubner, N. C., Poser, I., Cox, J., Nagaraj, N., Toyoda, Y., Gak, I. A., Weisswange, I., Mansfeld, J., Buchholz, F., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.053 · Cited by 1,270
Self-citationLocal Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase
Hernández-Vega, A., Braun, M., Scharrel, L., Jahnel, M., Wegmann, S., Hyman, B. T., Alberti, S., Diez, S., & Hyman, A. A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.042 · Cited by 395 · cited 1×
“If true, this would be another example of a cell using phase separation to raise protein concentration and uncover new chemistry, as has been proposed for polymer dynamics and enzymatic reactions (Banani et al., 2017; Hernández-Vega et al., 2017; Shin and Brangwynne, 2017; Woodruff et al., 2017).”
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Cited by
Alberti, S., Gladfelter, A., & Mittag, T. (2019) · Cell · doi:10.1016/j.cell.2018.12.035 · Cited by 2,856
Self-citationValence and patterning of aromatic residues determine the phase behavior of prion-like domains
Martin, E. W., Holehouse, A. S., Peran, I., Farag, M., Incicco, J. J., Bremer, A., Grace, C. R., Soranno, A., Pappu, R. V., & Mittag, T. (2020) · Science · doi:10.1126/science.aaw8653 · Cited by 1,147
Self-citationA framework for understanding the functions of biomolecular condensates across scales
Lyon, A. S., Peeples, W. B., & Rosen, M. K. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00303-z · Cited by 895
Stress granules and neurodegeneration
Wolozin, B., & Ivanov, P. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0222-5 · Cited by 810
Phase separation and neurodegenerative diseases: a disturbance in the force
Zbinden, A., Pérez-Berlanga, M., De Rossi, P., & Polymenidou, M. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.09.014 · Cited by 500
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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