Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles.
Bottom Line: These bodies are stabilized by patterned electrostatic interactions that are highly sensitive to temperature, ionic strength, arginine methylation, and splicing.Moreover, the bodies provide an alternative solvent environment that can concentrate single-stranded DNA but largely exclude double-stranded DNA.We propose that phase separation of disordered proteins containing weakly interacting blocks is a general mechanism for forming regulated, membraneless organelles.
Affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK.Show MeSH
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Mentions: A notable feature of Ddx4 disordered termini is that they arrange their charged residues into clustered blocks of net positive and negative charge (Figure 6Ai), resembling a block co-polymer. The clusters persist for approximately 8–10 residues in length and tend to contain 3–8 similarly charged residues. To determine the physical importance of this charge patterning, we produced a Ddx4 variant, Ddx4N1CS, with the same overall net charge, but in which the blocks were scrambled (Figure S6G). In Ddx4N1CS, the regions of opposing charge are removed while simultaneously maintaining the same overall isoelectric point (PI), amino acid composition, and positions of all other residues (Figure 6Aii). This construct was unable to form organelles in vitro under near-physiological conditions. When expressed in cells in the charge-scrambled form of Ddx4YFP, the protein accumulated to high concentrations without forming organelle-like structures (Figure 6Bii), revealing the importance of charge patterning in organelle formation.
Affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK.