8FSJ

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

8FSJ の概要

• エントリーDOI: 10.2210/pdb8fsj/pdb
• EMDBエントリー: 29419
• 分子名称: HCV E2 ectodomain, SYNZIP2 scaffold fusion, HEPC74 heavy chain, HEPC74 light chain, ... (9 entities in total)
• 機能のキーワード: hcv, e1e2, viral protein
• 由来する生物種: Hepacivirus C; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 180343.45

構造登録者

Metcalf, M.C.,Ofek, G. (登録日: 2023-01-10, 公開日: 2023-07-19, 最終更新日: 2024-10-23)

主引用文献

Metcalf, M.C.,Janus, B.M.,Yin, R.,Wang, R.,Guest, J.D.,Pozharski, E.,Law, M.,Mariuzza, R.A.,Toth, E.A.,Pierce, B.G.,Fuerst, T.R.,Ofek, G.
Structure of engineered hepatitis C virus E1E2 ectodomain in complex with neutralizing antibodies.
Nat Commun, 14:3980-3980, 2023

PubMed Abstract: 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.

PubMed: 37407593
DOI: 10.1038/s41467-023-39659-z

実験手法

ELECTRON MICROSCOPY (3.65 Å)