Sequence-specific polyampholyte phase separation in membraneless organelles

Abstract

Liquid-liquid phase separation of charge/aromatic-enriched intrinsically disordered proteins (IDPs) is critical in the biological function of membraneless organelles. Much of the physics of this recent discovery remains to be elucidated. Here we present a theory in the random phase approximation to account for electrostatic effects in polyampholyte phase separations, yielding predictions consistent with recent experiments on the IDP Ddx4. The theory is applicable to any charge pattern and thus provides a general analytical framework for studying sequence dependence of IDP phase separation.

5 pages, 3 figures; additional results; accepted for publication in PRL

Cited by in corpus (29)

• Comparative Roles of Charge, $\pi$ and Hydrophobic Interactions in Sequence-Dependent Phase Separation of Intrinsically Disordered Proteins
• Phase separation and single-chain compactness of charged disordered proteins are strongly correlated
• Model for disordered proteins with strongly sequence-dependent liquid phase behavior
• Random-phase-approximation theory for sequence-dependent, biologically functional liquid-liquid phase separation of intrinsically disordered proteins
• Charge Pattern Matching as a "Fuzzy" Mode of Molecular Recognition for the Functional Phase Separations of Intrinsically Disordered Proteins
• Coarse-Grained Residue-Based Models of Disordered Protein Condensates: Utility and Limitations of Simple Charge Pattern Parameters
• Thermodynamically Driven Assemblies and Liquid-liquid Phase Separations in Biology
• A Lattice Model of Charge-Pattern-Dependent Polyampholyte Phase Separation
• Minimalist design of polymer-oligopeptide hybrid as intrinsically disordered protein-mimicking scaffold for artificial membraneless organelle
• A unified analytical theory of heteropolymers for sequence-specific phase behaviors of polyelectrolytes and polyampholytes
• Conformational Heterogeneity and FRET Data Interpretation for Dimensions of Unfolded Proteins
• Analytical Formulation and Field-Theoretic Simulation of Sequence-Specific Phase Separation of Proteinlike Heteropolymers with Short- and Long-Spatial-Range Interactions
• Analytical Theory for Sequence-Specific Binary Fuzzy Complexes of Charged Intrinsically Disordered Proteins
• A Simple Explicit-Solvent Model of Polyampholyte Phase Behaviors and its Ramifications for Dielectric Effects in Biomolecular Condensates
• Subcompartmentalization of polyampholyte species in organelle-like condensates is promoted by charge pattern mismatch and strong excluded-volume interaction
• Theory and simulation of multiphase coexistence in biomolecular mixtures
• Assembly of Model Postsynaptic Densities Involves Interactions Auxiliary to Stoichiometric Binding
• Numerical Techniques for Applications of Analytical Theories to Sequence-Dependent Phase Separations of Intrinsically Disordered Proteins
• Electrostatics of Salt-Dependent Reentrant Phase Behaviors Highlights Diverse Roles of ATP in Biomolecular Condensates
• Differential Effects of Sequence-Local versus Nonlocal Charge Patterns on Phase Separation and Conformational Dimensions of Polyampholytes as Model Intrinsically Disordered Proteins
• Investigations of the Underlying Mechanisms of HIF-1α and CITED2 Binding to TAZ1
• Rheology and Viscoelasticity of Proteins and Nucleic Acids Condensates
• Emergence of multiphase condensates from a limited set of chemical building blocks
• Finite-size scaling analysis of protein droplet formation
• Phase behavior of blocky charge lattice polymers: Crystals, liquids, sheets, filaments and clusters
• Field theory description of ion association in re-entrant phase separation of polyampholytes
• Thermodynamically Consistent Phase-Field Theory Including Nearest-Neighbor Pair Correlations Explains Failure of Mean-Field Reasoning
• Counterion-controlled phase equilibria in a charge-regulated polymer solution
• Predicting Heteropolymer Phase Separation Using Two-Chain Contact Maps