Abstract:
:Cells are organized on length scales ranging from ångström to micrometres. However, the mechanisms by which ångström-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.
journal_name
Naturejournal_title
Natureauthors
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 MKdoi
10.1038/nature10879subject
Has Abstractpub_date
2012-03-07 00:00:00pages
336-40issue
7389eissn
0028-0836issn
1476-4687pii
nature10879journal_volume
483pub_type
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