Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein [article]

Christopher R. Carlson, Jonathan B. Asfaha, Chloe M. Ghent, Conor J. Howard, Nairi Hartooni, David O. Morgan
2020 biorxiv/medrxiv  
The nucleocapsid (N) protein of coronaviruses serves two major functions: compaction of the RNA genome in the virion and regulation of viral gene transcription in the infected cell. The N protein contains two globular RNA-binding domains surrounded by regions of intrinsic disorder. Phosphorylation of the central disordered region is required for normal viral genome transcription, which occurs in a cytoplasmic structure called the replication transcription complex (RTC). It is not known how
more » ... horylation controls N protein function. 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 structures that depend on multivalent RNA-protein and protein-protein interactions. Phosphorylation reduces a subset of these interactions, generating a more liquid-like droplet. We speculate 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. Inhibitors of N protein phosphorylation could therefore serve as antiviral therapy.
doi:10.1101/2020.06.28.176248 pmid:32637943 pmcid:PMC7337373 fatcat:it4z77jeebe3dhci4m6vx3zt4u