Exploring Relationships Between the Density of Charged Tracts Within Disordered Regions and Phase Separation

Ramiz Somjee^1,2, Diana M. Mitrea¹, Richard W. Kriwacki^1,3,*

¹Department of Structural Biology, St. Jude Children's Research Hospital
²Department of Chemistry, Rhodes College
³Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center
^*Corresponding author
Email: ramiz.somjee@stjude.org, diana.mitrea@stjude.org, richard.kriwacki@stjude.org

Pacific Symposium on Biocomputing 25:207-218(2020)

© 2020 World Scientific
Open Access chapter published by World Scientific Publishing Company and distributed under the terms of the Creative Commons Attribution (CC BY) 4.0 License.

Abstract

Biomolecular condensates form through a process termed phase separation and play diverse roles throughout the cell. Proteins that undergo phase separation often have disordered regions that can engage in weak, multivalent interactions; however, our understanding of the sequence grammar that defines which proteins phase separate is far from complete. Here, we show that proteins that display a high density of charged tracts within intrinsically disordered regions are likely to be constituents of electrostatically organized biomolecular condensates. We scored the human proteome using an algorithm termed ABTdensity that quantifies the density of charged tracts and observed that proteins with more charged tracts are enriched in particular Gene Ontology annotations and, based upon analysis of interaction networks, cluster into distinct biomolecular condensates. These results suggest that electrostatically-driven, multivalent interactions involving charged tracts within disordered regions serve to organize certain biomolecular condensates through phase separation.