8SIC

Crystal structure of Epstein-Barr virus glycoprotein 350 (gp350) in complex with Cy137C02, a monoclonal antibody isolated from macaques immunized with a gp350 nanoparticle vaccine

8SIC の概要

• エントリーDOI: 10.2210/pdb8sic/pdb
• 分子名称: Cy137C02 Fab heavy chain, Cy137C02 Fab light chain, Envelope glycoprotein gp350, ... (6 entities in total)
• 機能のキーワード: viral protein, envelope glycoprotein, monoclonal antibody, antiviral, immune system, macaques, epstein-barr virus, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Macaca fascicularis; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 190905.74

構造登録者

Joyce, M.G.,Jensen, J.L.,Chen, W.H.,Kanekiyo, M. (登録日: 2023-04-14, 公開日: 2024-04-17, 最終更新日: 2025-02-26)

主引用文献

Joyce, M.G.,Bu, W.,Chen, W.H.,Gillespie, R.A.,Andrews, S.F.,Wheatley, A.K.,Tsybovsky, Y.,Jensen, J.L.,Stephens, T.,Prabhakaran, M.,Fisher, B.E.,Narpala, S.R.,Bagchi, M.,McDermott, A.B.,Nabel, G.J.,Kwong, P.D.,Mascola, J.R.,Cohen, J.I.,Kanekiyo, M.
Structural basis for complement receptor engagement and virus neutralization through Epstein-Barr virus gp350.
Immunity, 58:295-, 2025

PubMed Abstract: Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with malignancies in humans. Viral infection of B cells is initiated by the viral glycoprotein 350 (gp350) binding to complement receptor 2 (CR2). Despite decades of effort, no vaccines or curative agents have been developed, partly due to lack of atomic-level understanding of the virus-host interface. Here, we determined the 1.7 Å structure of gp350 in complex with CR2. CR2 binding of gp350 utilized the same set of Arg residues required for recognition of its natural ligand, complement C3d. We further determined the structures of gp350 in complex with three potently neutralizing antibodies (nAbs) obtained from vaccinated macaques and EBV-infected individuals. Like the CR2 interaction, these nAbs targeted the acidic pocket within the CR2-binding site on gp350 using Arg residues. Our results illustrate two axes of molecular mimicry-gp350 versus C3d and CR2 versus EBV nAbs-offering insights for EBV vaccines and therapeutics development.

PubMed: 39909035
DOI: 10.1016/j.immuni.2025.01.010

実験手法

X-RAY DIFFRACTION (2.76 Å)