Ion binding with charge inversion combined with screening modulates DEAD box helicase phase transitions
Michael D. Crabtree,
Jack Holland,
Arvind S. Pillai,
Purnima S. Kompella,
Leon Babl,
Noah N. Turner,
James T. Eaton,
Georg K.A. Hochberg,
Dirk G.A.L. Aarts,
Christina Redfield,
Andrew J. Baldwin,
Timothy J. Nott
Affiliations
Michael D. Crabtree
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Jack Holland
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Arvind S. Pillai
Institute for Protein Design, University of Washington, Seattle, WA 98195, USA
Purnima S. Kompella
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Leon Babl
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Noah N. Turner
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
James T. Eaton
Department of Chemistry, Physical & Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK; Kavli Insititute of Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, Sherrington Rd, Oxford, OX1 3QU, UK
Georg K.A. Hochberg
Department of Chemistry, Philipps University Marburg, Hans-Meerwein-Straße 4, 35032 Marburg, Germany; Center for Synthetic Microbiology, Philipps University Marburg, Karl-von-Frisch-Straße 14, 35032 Marburg, Germany
Dirk G.A.L. Aarts
Department of Chemistry, Physical & Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK
Christina Redfield
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Andrew J. Baldwin
Department of Chemistry, Physical & Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK; Kavli Insititute of Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, Sherrington Rd, Oxford, OX1 3QU, UK; Corresponding author
Timothy J. Nott
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Corresponding author
Summary: Membraneless organelles, or biomolecular condensates, enable cells to compartmentalize material and processes into unique biochemical environments. While specific, attractive molecular interactions are known to stabilize biomolecular condensates, repulsive interactions, and the balance between these opposing forces, are largely unexplored. Here, we demonstrate that repulsive and attractive electrostatic interactions regulate condensate stability, internal mobility, interfaces, and selective partitioning of molecules both in vitro and in cells. We find that signaling ions, such as calcium, alter repulsions between model Ddx3 and Ddx4 condensate proteins by directly binding to negatively charged amino acid sidechains and effectively inverting their charge, in a manner fundamentally dissimilar to electrostatic screening. Using a polymerization model combined with generalized stickers and spacers, we accurately quantify and predict condensate stability over a wide range of pH, salt concentrations, and amino acid sequences. Our model provides a general quantitative treatment for understanding how charge and ions reversibly control condensate stability.
