8fsj

Cryo-EM structure of engineered hepatitis C virus E1E2 ectodomain in complex with antibodies AR4A, HEPC74, and IGH520

spinqualitylabelsall models 8fsj, resolution 3.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fsj is a 6 chain structure with sequence from Hepacivirus hominis, Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.65Å Ligands: BMA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A2P0NE15_9HEPC Publication Abstract from PubMed Hepatitis C virus (HCV) is a major global health burden as the leading causative agent of chronic liver disease and hepatocellular carcinoma. While the main antigenic target for HCV-neutralizing antibodies is the membrane-associated E1E2 surface glycoprotein, the development of effective vaccines has been hindered by complications in the biochemical preparation of soluble E1E2 ectodomains. Here, we present a cryo-EM structure of an engineered, secreted E1E2 ectodomain of genotype 1b in complex with neutralizing antibodies AR4A, HEPC74, and IGH520. Structural characterization of the E1 subunit and C-terminal regions of E2 reveal an overall architecture of E1E2 that concurs with that observed for non-engineered full-length E1E2. Analysis of the AR4A epitope within a region of E2 that bridges between the E2 core and E1 defines the structural basis for its broad neutralization. Our study presents the structure of an E1E2 complex liberated from membrane via a designed scaffold, one that maintains all essential structural features of native E1E2. The study advances the understanding of the E1E2 heterodimer structure, crucial for the rational design of secreted E1E2 antigens in vaccine development. Structure of engineered hepatitis C virus E1E2 ectodomain in complex with neutralizing antibodies.,Metcalf MC, Janus BM, Yin R, Wang R, Guest JD, Pozharski E, Law M, Mariuzza RA, Toth EA, Pierce BG, Fuerst TR, Ofek G Nat Commun. 2023 Jul 5;14(1):3980. doi: 10.1038/s41467-023-39659-z. PMID:37407593 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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