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Sequence Determinants of Intracellular Phase Separation by Complex Coacervation of a Disordered Protein
Journal article   Open access   Peer reviewed

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

Chi W Pak, Martyna Kosno, Alex S Holehouse, Shae B Padrick, Anuradha Mittal, Rustam Ali, Ali A Yunus, David R Liu, Rohit V Pappu and Michael K Rosen
Molecular cell, v 63(1)
07 Jul 2016
DOI: https://doi.org/10.1016/j.molcel.2016.05.042
PMID: 27392146
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.molcel.2016.05.042View
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Amino Acid Sequence Animals Cell Nucleus - chemistry Cell Nucleus - metabolism Computer Simulation HeLa Cells Humans Hydrophobic and Hydrophilic Interactions Intrinsically Disordered Proteins - chemistry Intrinsically Disordered Proteins - genetics Intrinsically Disordered Proteins - metabolism Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Mice Models, Molecular Mutation Organelles - chemistry Organelles - metabolism Protein Domains Proteomics - methods Static Electricity Structure-Activity Relationship Surface Properties Time Factors Transfection ESI Highly Cited Paper (Incites)
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 disordered protein, drives intracellular phase separation via complex coacervation, whereby the negatively charged NICD co-assembles with positively charged partners to form protein-rich dense liquid droplets. Mutagenesis reveals that the driving force for phase separation depends on the overall amino acid composition and not the precise sequence of NICD. Instead, phase separation is promoted by one or more regions of high negative charge density and aromatic/hydrophobic residues that are distributed across the protein. Many disordered proteins share similar sequence characteristics with NICD, suggesting that complex coacervation may be a widely used mechanism to promote intracellular phase separation.

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Highly Cited Paper 
Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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