8KHR

Cryo-EM structure of EBV gH/gL-gp42 in complex with fab 2C1

Summary for 8KHR

• Entry DOI: 10.2210/pdb8khr/pdb
• EMDB information: 37249
• Descriptor: Soluble gp42, 2C1 heavy chain, 2C1 light chain, ... (5 entities in total)
• Functional Keywords: human gammaherpesvirus 4, neutralizing antibody, viral protein/immune system, viral protein-immune system complex
• Biological source: Epstein-Barr virus (strain GD1) (HHV-4, Human herpesvirus 4); More
• Total number of polymer chains: 5
• Total formula weight: 130585.48

Authors

Fang, X.Y.,Zhao, G.X.,Zeng, M.S.,Liu, Z. (deposition date: 2023-08-22, release date: 2024-06-19, Last modification date: 2024-10-23)

Primary citation

Zhao, G.X.,Fang, X.Y.,Bu, G.L.,Chen, S.J.,Sun, C.,Li, T.,Xie, C.,Wang, Y.,Li, S.X.,Meng, N.,Feng, G.K.,Zhong, Q.,Kong, X.W.,Liu, Z.,Zeng, M.S.
Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.
Cell Rep Med, 5:101573-101573, 2024

PubMed Abstract: Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

PubMed: 38776874
DOI: 10.1016/j.xcrm.2024.101573

Experimental method

ELECTRON MICROSCOPY (3.25 Å)