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

Elias Honerød Augestad; Christina Holmboe Olesen; Christina Grønberg; Andreas Soerensen; Rodrigo Velázquez‐Moctezuma; Margherita Fanalista; Jens Bukh; Kaituo Wang; Pontus Emanuel Gourdon; Jannick C. Prentoe

doi:10.1101/2023.12.27.573427

Molecular BiologybioRxivDec 27, 2023

Preprint

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

Elias Honerød Augestad iD, Christina Holmboe Olesen iD, Christina Grønberg iD, Andreas Soerensen iD, Rodrigo Velázquez‐Moctezuma iD, Margherita Fanalista, Jens Bukh iD, Kaituo Wang iD, Pontus Emanuel Gourdon iD, Jannick C. Prentoe iD

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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