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Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):9929-9934. doi: 10.1073/pnas.1804177115. Epub 2018 Sep 14.

Relation between single-molecule properties and phase behavior of intrinsically disordered proteins.

Author information

1
Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015.
2
College of Integrative Sciences and Arts, Arizona State University, Mesa, AZ 85212.
3
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520.
4
Center for Materials Physics and Technology, Naval Research Laboratory, Washington, DC 20375.
5
Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015; jeetain@lehigh.edu.

Abstract

Proteins that undergo liquid-liquid phase separation (LLPS) have been shown to play a critical role in many physiological functions through formation of condensed liquid-like assemblies that function as membraneless organelles within biological systems. To understand how different proteins may contribute differently to these assemblies and their functions, it is important to understand the molecular driving forces of phase separation and characterize their phase boundaries and material properties. Experimental studies have shown that intrinsically disordered regions of these proteins are a major driving force, as many of them undergo LLPS in isolation. Previous work on polymer solution phase behavior suggests a potential correspondence between intramolecular and intermolecular interactions that can be leveraged to discover relationships between single-molecule properties and phase boundaries. Here, we take advantage of a recently developed coarse-grained framework to calculate the θ temperature [Formula: see text], the Boyle temperature [Formula: see text], and the critical temperature [Formula: see text] for 20 diverse protein sequences, and we show that these three properties are highly correlated. We also highlight that these correlations are not specific to our model or simulation methodology by comparing between different pairwise potentials and with data from other work. We, therefore, suggest that smaller simulations or experiments to determine [Formula: see text] or [Formula: see text] can provide useful insights into the corresponding phase behavior.

KEYWORDS:

intrinsically disordered proteins; liquid–liquid phase separation; membraneless organelles

PMID:
30217894
PMCID:
PMC6176625
DOI:
10.1073/pnas.1804177115
[Indexed for MEDLINE]
Free PMC Article

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