Structure of engineered hepatitis C virus E1E2 ectodomain in complex with neutralizing antibodies.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 07 2023
05 07 2023
Historique:
received:
27
01
2023
accepted:
22
06
2023
medline:
7
7
2023
pubmed:
6
7
2023
entrez:
5
7
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37407593
doi: 10.1038/s41467-023-39659-z
pii: 10.1038/s41467-023-39659-z
pmc: PMC10322937
doi:
Substances chimiques
Antibodies, Neutralizing
0
Epitopes
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3980Subventions
Organisme : NIAID NIH HHS
ID : R01 AI168048
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI168251
Pays : United States
Organisme : NIAID NIH HHS
ID : R24 AI158193
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132213
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI154100
Pays : United States
Informations de copyright
© 2023. The Author(s).
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