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• W3123197083 endingPage "e1009230" @default.
• W3123197083 startingPage "e1009230" @default.
• W3123197083 abstract "Hepatitis B virus (HBV) capsid or core protein (HBc) contains an N-terminal domain (NTD) and a C-terminal domain (CTD) connected by a short linker peptide. HBc plays a critical role in virtually every step of viral replication, which is further modulated by dynamic phosphorylation and dephosphorylation of its CTD. While several cellular kinases have been identified that mediate HBc CTD phosphorylation, there is little information on the cellular phosphatases that mediate CTD dephosphorylation. Herein, a consensus binding motif for the protein phosphatase 2A (PP2A) regulatory subunit B56 was recognized within the HBc linker peptide. Mutations within this motif designed to block or enhance B56 binding showed pleiotropic effects on CTD phosphorylation state as well as on viral RNA packaging, reverse transcription, and virion secretion. Furthermore, linker mutations affected the HBV nuclear episome (the covalently closed circular or CCC DNA) differentially during intracellular amplification vs. infection. The effects of linker mutations on CTD phosphorylation state varied with different phosphorylation sites and were only partially consistent with the linker motif serving to recruit PP2A-B56, specifically, to dephosphorylate CTD, suggesting that multiple phosphatases and/or kinases may be recruited to modulate CTD (de)phosphorylation. Furthermore, pharmacological inhibition of PP2A could decrease HBc CTD dephosphorylation and increase the nuclear HBV episome. These results thus strongly implicate the HBc linker in recruiting PP2A and other host factors to regulate multiple stages of HBV replication." @default.
• W3123197083 created "2021-02-01" @default.
• W3123197083 creator A5011350761 @default.
• W3123197083 creator A5018345618 @default.
• W3123197083 creator A5083483189 @default.
• W3123197083 date "2021-01-25" @default.
• W3123197083 modified "2023-10-18" @default.
• W3123197083 title "Multiple roles of PP2A binding motif in hepatitis B virus core linker and PP2A in regulating core phosphorylation state and viral replication" @default.
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• W3123197083 doi "https://doi.org/10.1371/journal.ppat.1009230" @default.
• W3123197083 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7861550" @default.
• W3123197083 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33493210" @default.
• W3123197083 hasPublicationYear "2021" @default.
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