Structural Organization of Pregenomic RNA and the Carboxy-Terminal Domain of the Capsid Protein of Hepatitis B Virus

The hepatitis b virus (hbv) double-stranded dna genome is reverse transcribed from its rna pregenome (pgrna) within the virus core (or capsid). phosphorylation of the arginine-rich carboxy-terminal domain (ctd) of the hbv capsid protein (cp183) is essential for pgrna encapsidation and reverse transcription. however,the structure of the ctd remains poorly defined. here we report sub-nanometer resolution cryo-em structures of in vitro assembled empty and pgrna-filled cp183 capsids in unphosphorylated and phosphorylation-mimic states. in empty capsids,we found unexpected evidence of surface accessible ctd density partially occluding pores in the capsid surface. we also observed that ctd organization changed substantively as a function of phosphorylation. in rna-filled capsids,unphosphorylated ctds favored thick ropes of rna,while the phosphorylation-mimic favored a mesh of thin,high-density strands suggestive of single stranded rna. these results demonstrate that the ctd can regulate nucleic acid structure,supporting the hypothesis that the hbv capsid has a functional role as a nucleic acid chaperone. © 2012 wang et al.