A kinase chaperones hepatitis B virus capsid assembly and captures capsid dynamics in vitro

The C-terminal domain (CTD) of Hepatitis B virus (HBV) core protein is involved in regulating multiple stages of the HBV lifecycle. CTD phosphorylation correlates with pregenomic-RNA encapsidation during capsid assembly, reverse transcription, and viral transport, although the mechanisms remain unkn...

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Bibliographic Details
Published in:PLoS pathogens 2011-11, Vol.7 (11), p.e1002388-e1002388
Main Authors: Chen, Chao, Wang, Joseph Che-Yen, Zlotnick, Adam
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biology
Capsid - metabolism
Capsid Proteins - metabolism
Health aspects
Hepatitis
Hepatitis B virus
Hepatitis B virus - physiology
Kinases
Microbiology
Molecular chaperones
Molecular Chaperones - metabolism
Molecular Sequence Data
Phosphorylation
Phosphotransferases
Physiological aspects
Protein-Serine-Threonine Kinases - metabolism
Protein-Serine-Threonine Kinases - physiology
Proteins
Viral Core Proteins - metabolism
Viral infections
Virus Assembly
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Summary:The C-terminal domain (CTD) of Hepatitis B virus (HBV) core protein is involved in regulating multiple stages of the HBV lifecycle. CTD phosphorylation correlates with pregenomic-RNA encapsidation during capsid assembly, reverse transcription, and viral transport, although the mechanisms remain unknown. In vitro, purified HBV core protein (Cp183) binds any RNA and assembles aggressively, independent of phosphorylation, to form empty and RNA-filled capsids. We hypothesize that there must be a chaperone that binds the CTD to prevent self-assembly and nonspecific RNA packaging. Here, we show that HBV capsid assembly is stalled by the Serine Arginine protein kinase (SRPK) binding to the CTD, and reactivated by subsequent phosphorylation. Using the SRPK to probe capsids, solution and structural studies showed that SRPK bound to capsid, though the CTD is sequestered on the capsid interior. This result indicates transient CTD externalization and suggests that capsid dynamics could be crucial for directing HBV intracellular trafficking. Our studies illustrate the stochastic nature of virus capsids and demonstrate the appropriation of a host protein by a virus for a non-canonical function.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1002388