Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins
- Washington University in St. Louis, United States
- University of Texas Southwestern Medical Center, United States
Abstract
Phase transitions of linear multivalent proteins control the reversible formation of many intracellular membraneless bodies. Specific non-covalent crosslinks involving domains / motifs lead to system-spanning networks referred to as gels. Gelation transitions can occur with or without phase separation. In gelation driven by phase separation multivalent proteins and their ligands condense into dense droplets, and gels form within droplets. System spanning networks can also form without a condensation or demixing of proteins into droplets. Gelation driven by phase separation requires lower protein concentrations, and seems to be the biologically preferred mechanism for forming membraneless bodies. Here, we use coarse-grained computer simulations and the theory of associative polymers to uncover the physical properties of intrinsically disordered linkers that determine the extent to which gelation of linear multivalent proteins is driven by phase separation. Our findings are relevant for understanding how sequence-encoded information in disordered linkers influences phase transitions of multivalent proteins.
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Funding
National Institutes of Health (RO1-GM56322)
- Michael K Rosen
National Science Foundation (MCB1614766)
- Rohit V Pappu
Howard Hughes Medical Institute
- Michael K Rosen
St. Jude Children's Research Hospital
- Rohit V Pappu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Harmon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins
eLife 6:e30294.
https://doi.org/10.7554/eLife.30294
