Publication Date:
2012-03-09
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343696/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343696/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- P30 CA142543/CA/NCI NIH HHS/ -- P41 GM103622/GM/NIGMS NIH HHS/ -- R01 GM056322/GM/NIGMS NIH HHS/ -- R01 GM056322-13/GM/NIGMS NIH HHS/ -- R01-GM088745/GM/NIGMS NIH HHS/ -- R01-GM56322/GM/NIGMS NIH HHS/ -- RR-08630/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 7;483(7389):336-40. doi: 10.1038/nature10879.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8812, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22398450" target="_blank"〉PubMed〈/a〉
Keywords:
Actin-Related Protein 2-3 Complex/metabolism
;
Adaptor Proteins, Signal Transducing/chemistry/metabolism
;
Binding Sites
;
Biopolymers/chemistry/metabolism
;
Fluorescence Recovery After Photobleaching
;
HeLa Cells
;
Humans
;
Ligands
;
Membrane Proteins/chemistry/metabolism
;
Multiprotein Complexes/*chemistry/*metabolism
;
Oncogene Proteins/chemistry/metabolism
;
*Phase Transition
;
Phosphorylation
;
Proline-Rich Protein Domains
;
Protein Structure, Quaternary
;
Proteins/*chemistry/*metabolism
;
*Signal Transduction
;
Wiskott-Aldrich Syndrome Protein, Neuronal/chemistry/metabolism
;
src Homology Domains
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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