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Sequence Determinants of Intracellular Phase Separation by Complex Coacervation of a Disordered Protein

Open access
Pak, Chi W., Kosno, Martyna, Holehouse, Alex S., Padrick, Shae B., Mittal, Anuradha, Ali, Rustam, Yunus, Ali A., Liu, David R., Pappu, Rohit V., Rosen, Michael K.·2016·Molecular Cell

Abstract

Summary Liquid-liquid phase separation, driven by collective interactions among multivalent and intrinsically disordered proteins, is thought to mediate the formation of membrane-less organelles in cells. Using parallel cellular and in vitro assays we show that the Nephrin intracellular domain (NICD), a disordered protein, drives intracellular phase separation via complex coacervation, whereby the negatively charged NICD co-assembles with positively charged partners to form protein-rich dense liquid droplets. Mutagenesis reveals that the driving force for phase separation depends on the overall amino acid composition and not the precise sequence of NICD. Instead, phase separation is promoted by one or more regions of high negative charge density and aromatic/hydrophobic residues that are distributed across the protein. Many disordered proteins share similar sequence characteristics with NICD, suggesting that complex coacervation may be a widely used mechanism to promote intracellular phase separation.

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Metadata

Authors
Pak, C. W., Kosno, M., Holehouse, A. S., Padrick, S. B., Mittal, A., Ali, R., Yunus, A. A., Liu, D. R., Pappu, R. V., & Rosen, M. K.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2016-07
Volume
63
Issue
1
Pages
72-85
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2467565876
Cited by
793
References
4
FWCI
28.44
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Sequence Determinants of Intracellular Phase Separation by Complex Coacervation of a Disordered Protein. https://app.cochat.ai/papers/10.1016/j.molcel.2016.05.042
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Pak, C. W., Kosno, M., Holehouse, A. S., Padrick, S. B., Mittal, A., Ali, R., Yunus, A. A., Liu, D. R., Pappu, R. V., & Rosen, M. K. (2016). Sequence Determinants of Intracellular Phase Separation by Complex Coacervation of a Disordered Protein. Molecular Cell. https://doi.org/10.1016/j.molcel.2016.05.042

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