9YJS

Crystal structure of anti-HCV human broad neutralizing antibody B098

Summary for 9YJS

• Entry DOI: 10.2210/pdb9yjs/pdb
• Descriptor: K400 fab heavy chain, K400 fab light chain (2 entities in total)
• Functional Keywords: immune system, viral protein-immune system complex, antiviral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 48533.13

Authors

Nguyen, T.K.Y.,Wilson, I.A. (deposition date: 2025-10-03, release date: 2026-07-01)

Primary citation

Chen, F.,Nguyen, Y.T.K.,Lee, Y.Z.,Giang, E.,Lau, S.C.,Koide, Y.,Hung, S.H.,Ueno, L.,He, L.,Fuerst, T.R.,Lauer, G.M.,Stanfield, R.L.,Zhu, J.,Wilson, I.A.,Law, M.
The conserved bridging domain on HCV E1E2 glycoprotein complex is targeted by neutralizing antibodies from diverse lineages.
Biorxiv, 2025

PubMed Abstract: The induction of potent and cross-reactive neutralizing antibody (nAb) responses remains a challenge in vaccine development against antigenically diverse viruses such as hepatitis C virus (HCV). The HCV E1E2 glycoprotein complex contains two major neutralizing sites: the neutralizing face (NF) and the less explored bridging domain (BD). Here, we characterized 25 BD-targeting nAbs isolated from infection or immunization. These antibodies arise from diverse B cell lineages but share convergent CDRH3 features. Epitope mapping by alanine scanning and negative-stain electron microscopy revealed overlapping epitopes on BD spanning antigenic regions AR4 and AR5, with variable back layer engagement. The crystal structure of a non-human primate BD nAb RM3-26 in complex with E2 uncovered a back layer-directed recognition mode analogous to that of the human nAb hcab40. Together, BD- and NF-directed nAbs exhibited additivity in their neutralization, highlighting BD as a conserved site of vulnerability on HCV and a valuable target for rational vaccine design.

PubMed: 41280117
DOI: 10.1101/2025.11.05.686883

Experimental method

X-RAY DIFFRACTION (2.78 Å)