7UR4

Cryo-EM Structure of the Neutralizing Antibody MPV467 in Complex with Prefusion Human Metapneumovirus F Glycoprotein

7UR4 の概要

• エントリーDOI: 10.2210/pdb7ur4/pdb
• EMDBエントリー: 26704
• 分子名称: Fusion glycoprotein F0, MPV467 Fab Heavy chain, MPV467 Fab Light chain, ... (5 entities in total)
• 機能のキーワード: neutralizing antibody, fusion protein, metapneumovirus, 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: 9
• 化学式量合計: 324493.77

構造登録者

Rush, S.A.,McLellan, J.S. (登録日: 2022-04-21, 公開日: 2022-06-08, 最終更新日: 2024-11-20)

主引用文献

Banerjee, A.,Huang, J.,Rush, S.A.,Murray, J.,Gingerich, A.D.,Royer, F.,Hsieh, C.L.,Tripp, R.A.,McLellan, J.S.,Mousa, J.J.
Structural basis for ultrapotent antibody-mediated neutralization of human metapneumovirus.
Proc.Natl.Acad.Sci.USA, 119:e2203326119-e2203326119, 2022

PubMed Abstract: Human metapneumovirus (hMPV) is a leading cause of morbidity and hospitalization among children worldwide, however, no vaccines or therapeutics are currently available for hMPV disease prevention and treatment. The hMPV fusion (F) protein is the sole target of neutralizing antibodies. To map the immunodominant epitopes on the hMPV F protein, we isolated a panel of human monoclonal antibodies (mAbs), and the mAbs were assessed for binding avidity, neutralization potency, and epitope specificity. We found the majority of the mAbs target diverse epitopes on the hMPV F protein, and we discovered multiple mAb binding approaches for antigenic site III. The most potent mAb, MPV467, which had picomolar potency, was examined in prophylactic and therapeutic mouse challenge studies, and MPV467 limited virus replication in mouse lungs when administered 24 h before or 72 h after viral infection. We determined the structure of MPV467 in complex with the hMPV F protein using cryo-electron microscopy to a resolution of 3.3 Å, which revealed a complex novel prefusion-specific epitope overlapping antigenic sites II and V on a single protomer. Overall, our data reveal insights into the immunodominant antigenic epitopes on the hMPV F protein, identify a mAb therapy for hMPV F disease prevention and treatment, and provide the discovery of a prefusion-specific epitope on the hMPV F protein.

PubMed: 35696580
DOI: 10.1073/pnas.2203326119

実験手法

ELECTRON MICROSCOPY (3.34 Å)