Phase transitions in the assembly of multivalent signalling proteins
Pilong Li,Sudeep Banjade,Hui-Chun Cheng,Soyeon Kim,Baoyu Chen,Liang Guo,Marc C. Llaguno,Javoris Hollingsworth,David S. King,Salman F. Banani,Paul S. Russo,Qiu-Xing Jiang,B. Tracy Nixon,Michael K. Rosen +13 more
TLDR
Interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid–liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution.Abstract:
Cells are organized on length scales ranging from angstrom to micrometres. However, the mechanisms by which angstrom-scale molecular properties are translated to micrometre-scale macroscopic properties are not well understood. Here we show that interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid-liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to the valency of the interacting species. In the case of the actin-regulatory protein called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its established biological partners NCK and phosphorylated nephrin, the phase transition corresponds to a sharp increase in activity towards an actin nucleation factor, the Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions may be used to spatially organize and biochemically regulate information throughout biology.read more
Citations
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Journal ArticleDOI
Biomolecular condensates: organizers of cellular biochemistry
TL;DR: This work has shown that liquid–liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates and has proposed a physical framework for this organizing principle.
Journal ArticleDOI
Liquid phase condensation in cell physiology and disease.
TL;DR: The findings together suggest that several membrane-less organelles have been shown to exhibit a concentration threshold for assembly, a hallmark of phase separation, and represent liquid-phase condensates, which form via a biologically regulated (liquid-liquid) phase separation process.
Journal ArticleDOI
Liquid-liquid phase separation in biology.
TL;DR: The basic physical concepts necessary to understand the consequences of liquid-like states for biological functions are discussed.
Journal ArticleDOI
A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation
Avinash Patel,Hyun O. Lee,Louise Jawerth,Shovamayee Maharana,Marcus Jahnel,Marco Y. Hein,Stoyno S. Stoynov,Julia Mahamid,Shambaditya Saha,Titus M. Franzmann,Andrej Pozniakovski,Ina Poser,Nicola Maghelli,Loic Royer,Martin Weigert,Eugene W. Myers,Stephan W. Grill,David N. Drechsel,Anthony A. Hyman,Simon Alberti +19 more
TL;DR: It is proposed that liquid-like compartments carry the trade-off between functionality and risk of aggregation and that aberrant phase transitions within liquid- like compartments lie at the heart of ALS and, presumably, other age-related diseases.
Journal ArticleDOI
Phase Separation by Low Complexity Domains Promotes Stress Granule Assembly and Drives Pathological Fibrillization
Amandine Molliex,Jamshid Temirov,Jihun Lee,Maura Coughlin,Anderson P. Kanagaraj,Hong Joo Kim,Tanja Mittag,J. Paul Taylor +7 more
TL;DR: It is demonstrated that the disease-related RBP hnRNPA1 undergoes liquid-liquid phase separation (LLPS) into protein-rich droplets mediated by a low complexity sequence domain (LCD), and suggested that LCD-mediated LLPS contributes to the assembly of stress granules and their liquid properties.
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