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Self-interaction of NPM1 modulates multiple mechanisms of liquid-liquid phase separation.
- Source :
-
Nature communications [Nat Commun] 2018 Feb 26; Vol. 9 (1), pp. 842. Date of Electronic Publication: 2018 Feb 26. - Publication Year :
- 2018
-
Abstract
- Nucleophosmin (NPM1) is an abundant, oligomeric protein in the granular component of the nucleolus with roles in ribosome biogenesis. Pentameric NPM1 undergoes liquid-liquid phase separation (LLPS) via heterotypic interactions with nucleolar components, including ribosomal RNA (rRNA) and proteins which display multivalent arginine-rich linear motifs (R-motifs), and is integral to the liquid-like nucleolar matrix. Here we show that NPM1 can also undergo LLPS via homotypic interactions between its polyampholytic intrinsically disordered regions, a mechanism that opposes LLPS via heterotypic interactions. Using a combination of biophysical techniques, including confocal microscopy, SAXS, analytical ultracentrifugation, and single-molecule fluorescence, we describe how conformational changes within NPM1 control valency and switching between the different LLPS mechanisms. We propose that this newly discovered interplay between multiple LLPS mechanisms may influence the direction of vectorial pre-ribosomal particle assembly within, and exit from the nucleolus as part of the ribosome biogenesis process.
- Subjects :
- Binding Sites
Cell Nucleolus metabolism
Cell Nucleolus ultrastructure
Cloning, Molecular
Escherichia coli genetics
Escherichia coli metabolism
Gene Expression
Genetic Vectors chemistry
Genetic Vectors metabolism
Humans
Intrinsically Disordered Proteins genetics
Intrinsically Disordered Proteins metabolism
Kinetics
Models, Molecular
Mutation
Nuclear Proteins genetics
Nuclear Proteins metabolism
Nucleophosmin
Organelle Biogenesis
Phase Transition
Protein Binding
Protein Interaction Domains and Motifs
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
Ribosomes genetics
Ribosomes metabolism
Static Electricity
Cell Nucleolus chemistry
Intrinsically Disordered Proteins chemistry
Nuclear Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 29483575
- Full Text :
- https://doi.org/10.1038/s41467-018-03255-3