Author information

¹Molecular Microbiology and Structural Biochemistry (MMSB) UMR 5086 CNRS/Université de Lyon, Labex Ecofect, 7 Passage du Vercors, 69367 Lyon, France.

²Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.

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.