8TOO

Crystal structure of Epstein-Barr virus gp42 in complex with antibody 4C12

8TOO の概要

• エントリーDOI: 10.2210/pdb8too/pdb
• 分子名称: 4C12 light chain, 4C12 heavy chain, Glycoprotein 42, ... (4 entities in total)
• 機能のキーワード: viral protein, antibody, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 258816.99

構造登録者

Bu, W.,Kumar, A.,Board, N.,Kim, J.,Dowdell, K.,Zhang, S.,Lei, Y.,Hostal, A.,Krogmann, T.,Wang, Y.,Pittaluga, S.,Marcotrigiano, J.,Cohen, J.I. (登録日: 2023-08-03, 公開日: 2024-03-27, 最終更新日: 2024-11-13)

主引用文献

Bu, W.,Kumar, A.,Board, N.L.,Kim, J.,Dowdell, K.,Zhang, S.,Lei, Y.,Hostal, A.,Krogmann, T.,Wang, Y.,Pittaluga, S.,Marcotrigiano, J.,Cohen, J.I.
Epstein-Barr virus gp42 antibodies reveal sites of vulnerability for receptor binding and fusion to B cells.
Immunity, 57:559-573.e6, 2024

PubMed Abstract: Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with B cell lymphomas. EBV glycoprotein 42 (gp42) binds HLA class II and activates membrane fusion with B cells. We isolated gp42-specific monoclonal antibodies (mAbs), A10 and 4C12, which use distinct mechanisms to neutralize virus infection. mAb A10 was more potent than the only known neutralizing gp42 mAb, F-2-1, in neutralizing EBV infection and blocking binding to HLA class II. mAb 4C12 was similar to mAb A10 in inhibiting glycoprotein-mediated B cell fusion but did not block receptor binding, and it was less effective in neutralizing infection. Crystallographic structures of gH/gL/gp42/A10 and gp42/4C12 complexes revealed two distinct sites of vulnerability on gp42 for receptor binding and B cell fusion. Passive transfer of mAb A10 into humanized mice conferred nearly 100% protection from viremia and EBV lymphomas after EBV challenge. These findings identify vulnerable sites on EBV that may facilitate therapeutics and vaccines.

PubMed: 38479361
DOI: 10.1016/j.immuni.2024.02.008

実験手法

X-RAY DIFFRACTION (2.6 Å)