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

Gregory L. Dignon, Wenwei Zheng, Robert B. Best, Young C. Kim, Jeetain Mittal

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 Tθ, the Boyle temperature TB, and the critical temperature Tc 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 Tθ or TB can provide useful insights into the corresponding phase behavior.

Original languageEnglish (US)
Pages (from-to)9929-9934
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number40
DOIs
StatePublished - Oct 2 2018
Externally publishedYes

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Intrinsically Disordered Proteins
Temperature
Proteins
Organelles
Polymers

Keywords

  • Intrinsically disordered proteins
  • Liquid-liquid phase separation
  • Membraneless organelles

ASJC Scopus subject areas

  • General

Cite this

Relation between single-molecule properties and phase behavior of intrinsically disordered proteins. / Dignon, Gregory L.; Zheng, Wenwei; Best, Robert B.; Kim, Young C.; Mittal, Jeetain.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 40, 02.10.2018, p. 9929-9934.

Research output: Contribution to journalArticle

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