Structure of engineered hepatitis C virus E1E2 ectodomain in complex with neutralizing antibodies

Matthew C. Metcalf, Benjamin M. Janus, Rui Yin, Ruixue Wang, Johnathan D. Guest, Edwin Pozharski, Mansun Law, Roy A. Mariuzza, Eric A. Toth, Brian G. Pierce, Thomas R. Fuerst and Gilad Ofek ()
Additional contact information
Matthew C. Metcalf: University of Maryland
Benjamin M. Janus: University of Maryland
Rui Yin: University of Maryland
Ruixue Wang: University of Maryland
Johnathan D. Guest: University of Maryland
Edwin Pozharski: University of Maryland
Mansun Law: The Scripps Research Institute
Roy A. Mariuzza: University of Maryland
Eric A. Toth: University of Maryland
Brian G. Pierce: University of Maryland
Thomas R. Fuerst: University of Maryland
Gilad Ofek: University of Maryland

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39659-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39659-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39659-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().