Sequence Determinants of Intracellular Phase Separation by Complex Coacervation of a Disordered Protein

• Published in: Molecular cell Vol. 63; no. 1; pp. 72 - 85
• Main Authors: Pak, Chi W., Kosno, Martyna, Holehouse, Alex S., Padrick, Shae B., Mittal, Anuradha, Ali, Rustam, Yunus, Ali A., Liu, David R., Pappu, Rohit V., Rosen, Michael K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.07.2016
• Subjects: amino acid composition; Amino Acid Sequence; Animals; Cell Nucleus - chemistry; Cell Nucleus - metabolism; Computer Simulation; droplets; HeLa Cells; Humans; Hydrophobic and Hydrophilic Interactions; hydrophobicity; in vitro studies; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - genetics; Intrinsically Disordered Proteins - metabolism; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Models, Molecular; mutagenesis; Mutation; organelles; Organelles - chemistry; Organelles - metabolism; Protein Domains; proteins; Proteomics - methods; separation; Static Electricity; Structure-Activity Relationship; Surface Properties; Time Factors; Transfection

Liquid-liquid phase separation, driven by collective interactions among multivalent and intrinsically disordered proteins, is thought to mediate the formation of membrane-less organelles in cells. Using parallel cellular and in vitro assays, we show that the Nephrin intracellular domain (NICD), a di...