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

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 (<sup>1</sup>H)-detected fast magic angle spinning solid-state NMR at highest magnetic field to characterize S-HDAg. We sequentially assigned <i>denovo</i> 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.

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Publication Details

Journal
Journal of the American Chemical Society
Published
2024-10-16
DOI
https://doi.org/10.1021/jacs.4c09409
Citations
3
Primary Topic
Hepatitis B Virus Studies
Type
article
Field-Weighted Citation Impact
1.16

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

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article

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

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article en
3 citations

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 (<sup>1</sup>H)-detected fast magic angle spinning solid-state NMR at highest magnetic field to characterize S-HDAg. We sequentially assigned <i>denovo</i> 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.

Journal of the American Chemical SocietyVol. 146(43)
Université Claude Bernard Lyon 1 (FR), Centre National de la Recherche Scientifique (FR), ETH Zurich (CH)
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, China Scholarship Council
Openalex Percentile: Top 19%
Hepatitis B Virus Studies
1.16
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