Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation

Significance The cell is divided into compartments where specific biochemical functions are performed. These compartments can be delineated by membranes or through phase separation of proteins or protein and nucleic acids to form membraneless organelles. The latter situation occurs with an intrinsically disordered region of Ddx4, a major constituent of germ granules. The nature of the interior of membraneless organelles is poorly understood. Here, we use NMR to show that the intrinsically disordered Ddx4 region remains disordered and highly dynamic in the phase-separated state, while diffusing as slowly as a particle the size of a bacterial cell. Ddx4 molecules form a network of interactions on phase separation, providing an alternative environment to that found in membrane-encapsulated organelles.