9PF9

X-ray crystal structure of ATX-350-2 Fab bound to Epstein-Barr virus glycoprotein 350

Summary for 9PF9

• Entry DOI: 10.2210/pdb9pf9/pdb
• Descriptor: Fab ATX-350-2 light chain, Fab ATX-350-2 heavy chain, BLLF1, ... (6 entities in total)
• Functional Keywords: viral protein, complex, antibody, ebv, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 98471.63

Authors

Lang, K.,Kher, G.,Aldridge, N.T.,Pancera, M. (deposition date: 2025-07-03, release date: 2025-12-24, Last modification date: 2026-03-04)

Primary citation

Chhan, C.B.,Lang, K.,Davis, A.R.,Wan, Y.H.,Aldridge, N.T.,Kher, G.,Scharffenberger, S.C.,Hardy, S.R.,Iureniev, R.,Giltiay, N.V.,Edwards, K.R.,Radtke, S.,Kiem, H.P.,Pancera, M.,McGuire, A.T.
Transgenic mouse-derived human monoclonal antibodies targeting EBV gp350 and gp42 provide basis for therapeutic development.
Cell Rep Med, 7:102618-102618, 2026

PubMed Abstract: Epstein-Barr virus (EBV) causes infectious mononucleosis and contributes to neurodegenerative disorders and malignancies, particularly in immune-compromised hosts. Transplant patients face high risk of post-transplant lymphoproliferative disease, a life-threatening EBV-driven lymphoma. There are no EBV-specific vaccines or treatments; however, neutralizing antibodies against EBV glycoproteins may offer utility as therapeutic agents. EBV entry into B cells involves gp350, which binds complement receptors, and gp42, which engages HLA class II to trigger fusion. Most existing monoclonal antibodies (mAbs) against these antigens are non-human, limiting clinical use. Using a transgenic mouse model, we generate two gp350 and eight gp42 genetically human neutralizing mAbs that block receptor binding. Structural analyses reveal extended sites of vulnerability relevant to vaccine development. Delivery of a gp42 mAb protects humanized mice from EBV challenge, while a gp350 mAb provides partial protection. These mAbs highlight the utility of transgenic mice to produce therapeutic mAbs for preventing EBV-driven disease.

PubMed: 41707657
DOI: 10.1016/j.xcrm.2026.102618

Experimental method

X-RAY DIFFRACTION (3.93 Å)