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bioRxiv · 10.1101/2023.12.27.573427

Structure of the hepatitis C virus E1/E2 envelope proteins in a homodimeric complex

Augestad, E.·Olesen, C. H.·Groenberg, C.·Soerensen, A.·Velazquez-Moctezuma, R.·Fanalista, M.·Bukh, J.·Wang, K.·Gourdon, P.·Prentoe, J.
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Abstract

Worldwide, 58 million individuals suffer from chronic hepatitis C virus (HCV) infection, a primary driver of liver cancer. The HCV envelope proteins, E1 and E2, form a heterodimer, which is the target for neutralizing antibodies. Despite high-resolution structural models of partial heterodimer elements, the structural landscape of higher-order E1/E2 oligomers remains unexplored. We determined a ~3.5 [A] cryo-electron microscopy structure of membrane-extracted HCV E1/E2 in a homodimeric arrangement. This structure includes detailed information on the homodimer interface, the E2-binding pocket for hypervariable region 1, antigenic site 412 conformation, and the organization of the E1/E2 transmembrane regions, including one internal to E1. This higher-order E1/E2 assembly could play a pivotal role in the design of novel vaccine antigens better mimicking E1/E2 complexes on the HCV particle.

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Augestad, E., Olesen, C. H., Groenberg, C., Soerensen, A., Velazquez-Moctezuma, R., Fanalista, M., Bukh, J., Wang, K., Gourdon, P., Prentoe, J.. 2023-12-27. Structure of the hepatitis C virus E1/E2 envelope proteins in a homodimeric complex. https://doi.org/10.1101/2023.12.27.573427

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