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Title | SRPK2 Mediates HBV Core Protein Phosphorylation and Capsid Assembly via Docking Interaction. |
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Journal, issue, pages | PLoS Pathog, Vol. 20, Issue 2, Page e1011978, Year 2024 |
Publish date | Feb 7, 2024 |
Authors | Ryan Pak Hong Yip / Doris Ching Ying Kwok / Louis Tung Faat Lai / Siu-Ming Ho / Ivan Chun Kit Wong / Chi-Ping Chan / Wilson Chun Yu Lau / Jacky Chi Ki Ngo / |
PubMed Abstract | Members of the serine-arginine protein kinase (SRPK) family, SRPK1 and SRPK2, phosphorylate the hepatitis B core protein (Cp) and are crucial for pregenomic RNA encapsidation during viral ...Members of the serine-arginine protein kinase (SRPK) family, SRPK1 and SRPK2, phosphorylate the hepatitis B core protein (Cp) and are crucial for pregenomic RNA encapsidation during viral nucleocapsid assembly. Among them, SRPK2 exhibits higher kinase activity toward Cp. In this study, we identified Cp sites that are phosphorylated by SRPK2 and demonstrated that the kinase utilizes an SRPK-specific docking groove to interact with and regulate the phosphorylation of the C-terminal arginine rich domain of Cp. We determined that direct interaction between the docking groove of SRPK2 and unphosphorylated Cp inhibited premature viral capsid assembly in vitro, whereas the phosphorylation of the viral protein reactivated the process. Pull-down assays together with the new cryo-electron microscopy structure of the HBV capsid in complex with SRPK2 revealed that the kinases decorate the surface of the viral capsid by interacting with the C-terminal domain of Cp, underscoring the importance of the docking interaction in regulating capsid assembly and pregenome packaging. Moreover, SRPK2-knockout in HepG2 cells suppressed Cp phosphorylation, indicating that SRPK2 is an important cellular kinase for HBV life cycle. |
External links | PLoS Pathog / PubMed:38324561 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.4 - 11.0 Å |
Structure data | EMDB-37631: Hepatitis B virus capsid (HBV core protein) EMDB-37634: SR protein kinase 2 bound at 2-fold vertex of Hepatitis B virus capsid EMDB-38062: Hepatitis B virus capsid in complex with SR protein kinase 2 |
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