Phosphoregulation of Phase Separation by the SARS-CoV-2 N Protein Suggests a Biophysical Basis for its Dual Functions
| Autor: | Christopher R. Carlson, Nairi Hartooni, Chloe M. Ghent, David O. Morgan, Maliheh Safari, Alan D. Frankel, Jonathan B. Asfaha, Conor J Howard |
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| Rok vydání: | 2020 |
| Předmět: |
viruses
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Protein domain nucleocapsid Biology medicine.disease_cause Medical and Health Sciences Oligomer Genome N protein 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Transcription (biology) medicine Molecular Biology 030304 developmental biology Coronavirus 0303 health sciences SARS-CoV-2 phosphorylation COVID-19 RNA Cell Biology Biological Sciences Cell biology chemistry Phosphorylation biomolecular condensate phase separation 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Molecular cell, vol 80, iss 6 Molecular Cell |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2020.11.025 |
| Popis: | The nucleocapsid (N) protein of coronaviruses serves two major functions: compaction of the RNA genome in the virion and regulation of viral gene transcription. It is not clear how the N protein mediates such distinct functions. The N protein contains two RNA-binding domains surrounded by regions of intrinsic disorder. Phosphorylation of the central disordered region promotes the protein's transcriptional function, but the underlying mechanism is not known. Here, we show that the N protein of SARS-CoV-2, together with viral RNA, forms biomolecular condensates. Unmodified N protein forms partially ordered gel-like condensates and discrete 15-nm particles based on multivalent RNA-protein and protein-protein interactions. Phosphorylation reduces these interactions, generating a more liquid-like droplet. We propose that distinct oligomeric states support the two functions of the N protein: unmodified protein forms a structured oligomer that is suited for nucleocapsid assembly, and phosphorylated protein forms a liquid-like compartment for viral genome processing. |
| Databáze: | OpenAIRE |
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