Sequence dependent phase separation of protein-polynucleotide mixtures elucidated using molecular simulations
-
- Roshan Mammen Regy
- Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015, USA
-
- Gregory L Dignon
- Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015, USA
-
- Wenwei Zheng
- College of Integrative Sciences and Arts, Arizona State University, Mesa, AZ 85212, USA
-
- Young C Kim
- Center for Materials Physics and Technology, Naval Research Laboratory, Washington, DC 20375, USA
-
- Jeetain Mittal
- Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015, USA
抄録
<jats:title>Abstract</jats:title><jats:p>Ribonucleoprotein (RNP) granules are membraneless organelles (MLOs), which majorly consist of RNA and RNA-binding proteins and are formed via liquid–liquid phase separation (LLPS). Experimental studies investigating the drivers of LLPS have shown that intrinsically disordered proteins (IDPs) and nucleic acids like RNA and other polynucleotides play a key role in modulating protein phase separation. There is currently a dearth of modelling techniques which allow one to delve deeper into how polynucleotides play the role of a modulator/promoter of LLPS in cells using computational methods. Here, we present a coarse-grained polynucleotide model developed to fill this gap, which together with our recently developed HPS model for protein LLPS, allows us to capture the factors driving protein-polynucleotide phase separation. We explore the capabilities of the modelling framework with the LAF-1 RGG system which has been well studied in experiments and also with the HPS model previously. Further taking advantage of the fact that the HPS model maintains sequence specificity we explore the role of charge patterning on controlling polynucleotide incorporation into condensates. With increased charge patterning we observe formation of structured or patterned condensates which suggests the possible roles of polynucleotides in not only shifting the phase boundaries but also introducing microscopic organization in MLOs.</jats:p>
収録刊行物
-
- Nucleic Acids Research
-
Nucleic Acids Research 48 (22), 12593-12603, 2020-12-02
Oxford University Press (OUP)