Structural comparisons of hepatitis B core antigen particles with different C-terminal lengths

Area of Science:

• Virology
• Structural Biology
• Biochemistry

Background:

• Hepatitis B virus (HBV) replication involves the encapsidation of its RNA genome by the HBV core protein (HBcAg).
• The C-terminal region of HBcAg is known to be involved in interactions with the viral RNA.
• Understanding the structural basis of RNA encapsidation is crucial for developing antiviral strategies.

Purpose of the Study:

• To investigate the role of C-terminal tail length of HBV core protein in the self-assembly of HBcAg particles.
• To elucidate the structural basis of RNA encapsidation by HBcAg particles with different C-terminal lengths.
• To determine how C-terminal variations affect the RNA content and genome packaging.

Main Methods:

• Recombinant HBcAg particles were generated using core proteins with varying C-terminal lengths (residues 154, 164, 167, and 183).
• Cryo-electron microscopy (cryoEM) was employed to determine the three-dimensional structures of these assembled particles.
• Structural comparisons were performed to analyze differences in capsid structure and RNA content.

Main Results:

• HBcAg particles with different C-terminal lengths self-assembled into stable structures.
• CryoEM analysis revealed highly similar capsid structures across all tested C-terminal variants.
• A positive correlation was observed between the length of the C-terminal tail and the amount of encapsulated RNA.

Conclusions:

• The C-terminal tail of HBV core protein plays a significant role in determining the extent of RNA encapsidation.
• Retention of more amino acid residues at the C-terminus leads to increased RNA content within HBcAg particles.
• The basic C-terminal tail is a key determinant of HBV genome size during the encapsidation process.