Multiple roles of PP2A binding motif in hepatitis B virus core linker and PP2A in regulating core phosphorylation state and viral replication
Fig 13
Model of interactions between HBc linker and host protein phosphatase (kinase) in regulating multiple steps of viral replication.
The HBc domains (NTD, linker, CTD) are shown in the middle as horizontal boxes, with the linker sequence highlighted. Also highlighted are the last residue of NTD (L140, part of the PP2A-B56 consensus binding motif) and the three CTD sites where phosphorylation state was monitored in this study. The linker sequence is proposed to regulate dynamic CTD phosphorylation and dephosphorylation to control different stages of viral replication, among other mechanisms. The red and green arrows on the top denote the recruitment of cellular phosphatase (PP) and kinase (KI), respectively, by the indicated linker/NTD sites to modulate the indicated CTD phosphorylation sites. Shown at the bottom is a simplified scheme of HBV replication cycle, with the different stages affected by the different CTD phosphorylation sites and PP2A/CDK2 highlighted. The stimulatory and inhibitory effects of certain linker mutations on CCC DNA formation during intracellular amplification and infection, respectively, are denoted by the green and red arrows. See text for details.