title: A kinase chaperones hepatitis B virus capsid assembly and captures capsid dynamics in vitro.
abstract: 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.
authors: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, United States of America.
authors: Chao
authors: C
authors: Chen
authors: Joseph Che-Yen
authors: JC
authors: Wang
authors: Adam
authors: A
authors: Zlotnick
mesh_terms: D000595:Amino Acid Sequence; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology*; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D014758:Viral Core Proteins / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins; D018832:Molecular Chaperones; D014758:Viral Core Proteins; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases; C110522:SRPK2 protein, human