Hepatitis Delta Antigen Retains the Assembly Domain as the Only Rigid Entity

J Am Chem Soc. 2024 Oct 30;146(43):29531-29539. doi: 10.1021/jacs.4c09409. Epub 2024 Oct 16.

Abstract

The hepatitis delta virus (HDV) S-HDAg and L-HDAg antigens are the two isoforms of the single protein encoded by the viral genome. Together with the double-stranded RNA genome they form the HDV ribonucleoprotein (RNP) complex. In the context of a divide-and-conquer approach, we used a combination of cell-free protein synthesis and proton (1H)-detected fast magic angle spinning solid-state NMR at highest magnetic field to characterize S-HDAg. We sequentially assigned denovo its isolated N-terminal assembly domain using less than 1 mg of fully protonated protein. Our results show that the assembly domain is the sole rigid component in S-HDAg, with its structure remaining fully conserved within the full-length protein. In contrast, the rest of the protein remains dynamic. This work provides the necessary foundation for future studies of the viral RNP.

MeSH terms

  • Hepatitis Delta Virus* / chemistry
  • Hepatitis delta Antigens* / chemistry
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Domains

Substances

  • Hepatitis delta Antigens