Article ; Online: SRPK2 Mediates HBV Core Protein Phosphorylation and Capsid Assembly via Docking Interaction.
2024 Volume 20, Issue 2, Page(s) e1011978
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 nucleocapsid assembly. Among them, SRPK2 exhibits higher kinase ... ...
| 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 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. |
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| MeSH term(s) | Phosphorylation ; Capsid/metabolism ; Hepatitis B virus/metabolism ; Cryoelectron Microscopy ; Protein Serine-Threonine Kinases/metabolism ; Capsid Proteins/metabolism ; Virus Assembly/physiology ; Arginine/metabolism |
| Chemical Substances | Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Capsid Proteins ; Arginine (94ZLA3W45F) |
| Language | English |
| Publishing date | 2024-02-07 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2205412-1 |
| ISSN | 1553-7374 ; 1553-7374 |
| ISSN (online) | 1553-7374 |
| ISSN | 1553-7374 |
| DOI | 10.1371/journal.ppat.1011978 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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