9O3D

Crystal structure of broadly neutralizing antibody HEPC108 in complex with Hepatitis C virus envelope glycoprotein E2 ectodomain

Summary for 9O3D

• Entry DOI: 10.2210/pdb9o3d/pdb
• Descriptor: HEPC108 Fab Heavy Chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, HEPC108 Fab Light Chain, ... (11 entities in total)
• Functional Keywords: hcv glycoprotein, broadly neutralizing antibodies, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 323629.41

Authors

Flyak, A.I.,Wilcox, X.E. (deposition date: 2025-04-07, release date: 2026-01-21, Last modification date: 2026-02-18)

Primary citation

Wilcox, X.E.,Punia, R.,Mimms, J.,Frumento, N.,Bailey, J.R.,Flyak, A.I.
Structural repertoire of HCV broadly neutralizing antibodies targeting the E2 front layer supersite.
Structure, 2026

PubMed Abstract: Structural studies of the hepatitis C virus (HCV) E2 glycoprotein in complex with broadly neutralizing antibodies (bNAbs) have been instrumental in mapping neutralizing epitopes and guiding the rational design of immunogens. However, the robust structural classification of HCV bNAbs is lacking, complicating immunogen design. The majority of HCV bNAbs recognize the E2 front layer (FRLY) supersite. Here, we developed a roadmap for the structural classification of FRLY-specific bNAbs. We discovered three distinct structural classes, each utilizing a unique binding mode to engage the FRLY supersite. HCV strains with multiple FRLY polymorphisms had a profound impact on the binding and neutralization of bNAbs from distinct FRLY classes. Our findings establish the FRLY as a major antigenic supersite targeted by three bNAb classes and underscore the intrinsic structural plasticity of V1-69-encoded HCV bNAbs.

PubMed: 41633361
DOI: 10.1016/j.str.2026.01.005

Experimental method

X-RAY DIFFRACTION (2.68 Å)