Temperature-Controlled Liquid-Liquid Phase Separation of Disordered Proteins

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) is a commonly observed phenomenon within the cell, and such condensates are also highly attractive for applications in biomaterials and drug delivery. A better understanding of the sequence-dependent thermoresponsive behavior is of immense interest as it will aid in the design of protein sequences with desirable properties and in the understanding of cellular response to heat stress. In this work, we use a transferable coarse-grained model to directly probe the sequence-dependent thermoresponsive phase behavior of IDPs. To achieve this goal, we develop a unique knowledge-based amino acid potential that accounts for the temperature-dependent effects on solvent-mediated interactions for different types of amino acids. Remarkably, we are able to distinguish between more than 35 IDPs with upper or lower critical solution temperatures at experimental conditions, thus providing direct evidence that incorporating the temperature-dependent solvent-mediated interactions to IDP assemblies can capture the difference in the shape of the resulting phase diagrams. Given the success of the model in predicting experimental behavior, we use it as a high-throughput screening framework to scan through millions of disordered sequences to characterize the composition dependence of protein phase separation.

Original languageEnglish (US)
JournalACS Central Science
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Intrinsically Disordered Proteins
Phase separation
Proteins
Liquids
Amino Acids
Temperature
Amino acids
Biocompatible Materials
Phase behavior
Drug delivery
Phase diagrams
Screening
Throughput
Biomaterials
Chemical analysis

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Temperature-Controlled Liquid-Liquid Phase Separation of Disordered Proteins. / Dignon, Gregory L.; Zheng, Wenwei; Kim, Young C.; Mittal, Jeetain.

In: ACS Central Science, 01.01.2019.

Research output: Contribution to journalArticle

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