Phase Transitions in the Assembly of Multi-Valent Signaling Proteins
Cells are organized on length scales ranging from Angstroms to microns. However, the mechanisms by which Angstrom-scale molecular properties are translated to micron-scale macroscopic properties are not well understood. Here we show that interactions between diverse, synthetic multivalent macromolec...
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| Published in: | Nature (London) Vol. 483; no. 7389; pp. 336 - 340 |
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| Main Authors: | , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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07-03-2012
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| Online Access: | Get full text |
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| Abstract | Cells are organized on length scales ranging from Angstroms to microns. However, the mechanisms by which Angstrom-scale molecular properties are translated to micron-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 micron-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 valency of the interacting species. In the case of the actin regulatory protein, neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) interacting with its established biological partners Nck and phosphorylated nephrin
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, the phase transition corresponds to a sharp increase in activity toward the actin nucleation factor, 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 are likely used to spatially organize and biochemically regulate information throughout biology. |
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| AbstractList | Cells are organized on length scales ranging from Angstroms to microns. However, the mechanisms by which Angstrom-scale molecular properties are translated to micron-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 micron-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 valency of the interacting species. In the case of the actin regulatory protein, neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) interacting with its established biological partners Nck and phosphorylated nephrin
1
, the phase transition corresponds to a sharp increase in activity toward the actin nucleation factor, 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 are likely used to spatially organize and biochemically regulate information throughout biology. |
| Author | Jiang, Qiu-Xing Russo, Paul S. Banjade, Sudeep Chen, Baoyu Nixon, B. Tracy King, David S. Llaguno, Marc Cheng, Hui-Chun Hollingsworth, Javoris V. Guo, Liang Li, Pilong Rosen, Michael K. Kim, Soyeon Banani, Salman F. |
| AuthorAffiliation | 1 Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA 2 BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA 6 Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA 5 Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA 3 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA 4 Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA |
| AuthorAffiliation_xml | – name: 1 Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA – name: 3 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA – name: 6 Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – name: 2 BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA – name: 5 Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA – name: 4 Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA |
| Author_xml | – sequence: 1 givenname: Pilong surname: Li fullname: Li, Pilong organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – sequence: 2 givenname: Sudeep surname: Banjade fullname: Banjade, Sudeep organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – sequence: 3 givenname: Hui-Chun surname: Cheng fullname: Cheng, Hui-Chun organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, 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University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – sequence: 6 givenname: Liang surname: Guo fullname: Guo, Liang organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – sequence: 7 givenname: Marc surname: Llaguno fullname: Llaguno, Marc organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – sequence: 8 givenname: Javoris V. surname: Hollingsworth fullname: Hollingsworth, Javoris V. organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – sequence: 9 givenname: David S. surname: King fullname: King, David S. organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – sequence: 10 givenname: Salman F. surname: Banani fullname: Banani, Salman F. organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and 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Tracy surname: Nixon fullname: Nixon, B. Tracy organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA – sequence: 14 givenname: Michael K. surname: Rosen fullname: Rosen, Michael K. organization: Department of Biochemistry and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390-8812, USA BioCAT of IIT at the Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA Howard Hughes Medical Institute Mass Spectrometry Laboratory and Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA |
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| Title | Phase Transitions in the Assembly of Multi-Valent Signaling Proteins |
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