Phase transitions in the assembly of multivalent signalling proteins

Pilong Li, Sudeep Banjade, Hui Chun Cheng, Soyeon Kim, Baoyu Chen, Liang Guo, Marc Llaguno, Javoris V. Hollingsworth, David S. King, Salman F. Banani, Paul S. Russo, Qiu Xing Jiang, B. Tracy Nixon, Michael K. Rosen

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Abstract

Cells are organized on length scales ranging from ångström to micrometres. However, the mechanisms by which ängström-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.

Original languageEnglish (US)
Pages (from-to)336-340
Number of pages5
JournalNature
Volume483
Issue number7389
DOIs
StatePublished - Mar 15 2012

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Phase Transition
Actins
Wiskott-Aldrich Syndrome Protein
Actin-Related Protein 2-3 Complex
Proteins
Polymers
Phosphotransferases
Phosphorylation
RNA
nephrin

ASJC Scopus subject areas

  • General

Cite this

Li, P., Banjade, S., Cheng, H. C., Kim, S., Chen, B., Guo, L., ... Rosen, M. K. (2012). Phase transitions in the assembly of multivalent signalling proteins. Nature, 483(7389), 336-340. https://doi.org/10.1038/nature10879

Phase transitions in the assembly of multivalent signalling proteins. / Li, Pilong; Banjade, Sudeep; Cheng, Hui Chun; Kim, Soyeon; Chen, Baoyu; Guo, Liang; Llaguno, Marc; Hollingsworth, Javoris V.; King, David S.; Banani, Salman F.; Russo, Paul S.; Jiang, Qiu Xing; Nixon, B. Tracy; Rosen, Michael K.

In: Nature, Vol. 483, No. 7389, 15.03.2012, p. 336-340.

Research output: Contribution to journalArticle

Li, P, Banjade, S, Cheng, HC, Kim, S, Chen, B, Guo, L, Llaguno, M, Hollingsworth, JV, King, DS, Banani, SF, Russo, PS, Jiang, QX, Nixon, BT & Rosen, MK 2012, 'Phase transitions in the assembly of multivalent signalling proteins', Nature, vol. 483, no. 7389, pp. 336-340. https://doi.org/10.1038/nature10879
Li P, Banjade S, Cheng HC, Kim S, Chen B, Guo L et al. Phase transitions in the assembly of multivalent signalling proteins. Nature. 2012 Mar 15;483(7389):336-340. https://doi.org/10.1038/nature10879
Li, Pilong ; Banjade, Sudeep ; Cheng, Hui Chun ; Kim, Soyeon ; Chen, Baoyu ; Guo, Liang ; Llaguno, Marc ; Hollingsworth, Javoris V. ; King, David S. ; Banani, Salman F. ; Russo, Paul S. ; Jiang, Qiu Xing ; Nixon, B. Tracy ; Rosen, Michael K. / Phase transitions in the assembly of multivalent signalling proteins. In: Nature. 2012 ; Vol. 483, No. 7389. pp. 336-340.
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