Fig. 9
From: Liquid–liquid phase separation in human health and diseases
LLPS in SARS-CoV-2 infection. a Nucleocapsid (N) protein contains an N-terminal intrinsically disordered region (N-IDR), a structured N-terminal domain (NTD), a central intrinsically disordered region (central-IDR), a structured C-terminal domain (CTD), and a C-terminal intrinsically disordered region (C-IDR). Of these, NTD and central-IDR play an important role in the phase separation of N protein with RNA. b LLPS plays an important role in SARS-CoV-2 infection. The central-IDR contains a conserved serine-arginine (SR)-rich sequence. Unmodified N protein forms gel-like condensates containing discrete ribonucleoprotein (RNP), which is conducive to its function of genome packaging roles. After being phosphorylated by cyclin-dependent kinase-1 (CDK1) and glycogen synthase kinase-3 (GSK3) in the SR region, N protein forms liquid-like condensates for viral genome processing. Viral RNA sequence and structure in specific genomic regions are also involved in the regulation of the N protein phase separation. The specific regions of the viral RNA genome, including a region spanning the 5’ end (first 1000 nt) and a region-encoded N protein at the 3᾽ end, can promote the phase separation of N proteins, whereas most regions in the genome facilitate the dissolution of N protein condensates. The viral membrane (M) protein can independently form condensates with N protein. During the late stages of SARS-CoV-2 infection, the viral RNP condensates will interact with the soluble CTD of M protein to form two-layered condensates, which promote the SARS-CoV-2 virion assembly
