The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
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.
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