9B2C

Structure of the Porcine deltacoronavirus (PDCoV) receptor-binding domain bound to the PD33 antibody Fab fragment and the Kappa light chain nanobody

9B2C の概要

• エントリーDOI: 10.2210/pdb9b2c/pdb
• EMDBエントリー: 44103
• 分子名称: Spike glycoprotein, PD33 Fab kappa light chain, Kappa light chain nanobody, ... (6 entities in total)
• 機能のキーワード: spike glycoprotein, fusion protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral neutralization, inhibitor, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Porcine deltacoronavirus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 83787.64

構造登録者

Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (登録日: 2024-03-14, 公開日: 2024-11-13, 最終更新日: 2024-12-18)

主引用文献

Rexhepaj, M.,Asarnow, D.,Perruzza, L.,Park, Y.J.,Guarino, B.,Mccallum, M.,Culap, K.,Saliba, C.,Leoni, G.,Balmelli, A.,Yoshiyama, C.N.,Dickinson, M.S.,Quispe, J.,Brown, J.T.,Tortorici, M.A.,Sprouse, K.R.,Taylor, A.L.,Corti, D.,Starr, T.N.,Benigni, F.,Veesler, D.
Isolation and escape mapping of broadly neutralizing antibodies against emerging delta-coronaviruses.
Immunity, 57:2914-2927.e7, 2024

PubMed Abstract: Porcine delta-coronavirus (PDCoV) spillovers were recently detected in febrile children, underscoring the recurrent zoonoses of divergent CoVs. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated PDCoV spike (S)-directed monoclonal antibodies (mAbs) from humanized mice and found that two, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryoelectron microscopy (cryo-EM) structures of PD33 and PD41 in complex with the S receptor-binding domain (RBD) and ectodomain trimer revealed the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs competitively interfere with host aminopeptidase N binding to neutralize PDCoV and used deep-mutational scanning epitope mapping to associate RBD antigenic sites with mAb-mediated neutralization potency. Our results indicate a PD33-PD41 mAb cocktail may heighten the barrier to escape. PD33 and PD41 are candidates for clinical advancement against future PDCoV outbreaks.

PubMed: 39488210
DOI: 10.1016/j.immuni.2024.10.001

実験手法

ELECTRON MICROSCOPY (3 Å)