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: The internal order within the organelles was assessed using fluorescence recovery after photobleaching (FRAP) measurements. The half time to recovery of the fluorescence signal of a photo-bleached body of diameter 1.5 μm took approximately 2.5 s at 37°C (Figure 2A), corresponding to an approximate diffusion coefficient of 3 ± 1 × 10−13 m2 s−1, a value two orders of magnitude lower than that measured for free globular proteins of a similar size as determined by both FRAP and NMR (Figure S5B). These self-diffusion rates are consistent with those of other non-membrane organelles, such as nuclear speckles and nucleoli (Phair and Misteli 2000). While the observed diffusion within the droplets is substantially slower than the motion of free protein, the interior is nevertheless highly mobile, consistent with weak interactions between Ddx4 proteins within the droplet.
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.