8CW9

Prefusion-stabilized hMPV fusion protein bound to ADI-61026 and MPE8 Fabs

8CW9 の概要

• エントリーDOI: 10.2210/pdb8cw9/pdb
• EMDBエントリー: 27024
• 分子名称: Fusion glycoprotein F0, MPE8 light chain, ADI-61026 heavy, ... (6 entities in total)
• 機能のキーワード: site 0 neutralizing antibody, prefusion-stabilized hmpv f protein, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human metapneumovirus; 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 541479.03

構造登録者

Hsieh, C.-L.,McLellan, J.S. (登録日: 2022-05-18, 公開日: 2022-08-10, 最終更新日: 2025-05-28)

主引用文献

Rappazzo, C.G.,Hsieh, C.L.,Rush, S.A.,Esterman, E.S.,Delgado, T.,Geoghegan, J.C.,Wec, A.Z.,Sakharkar, M.,Mas, V.,McLellan, J.S.,Walker, L.M.
Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein.
Immunity, 55:1710-1724.e8, 2022

PubMed Abstract: Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens.

PubMed: 35944529
DOI: 10.1016/j.immuni.2022.07.003

実験手法

ELECTRON MICROSCOPY (3.46 Å)