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9DEZ

PDCoV S trimer bound by three copies of PD41 Fab

Summary for 9DEZ
Entry DOI10.2210/pdb9dez/pdb
EMDB information46804 46805 46806 46814 46815 46816
DescriptorSpike glycoprotein, PD41 Fab variable heavy-chain, PD41 Fab variable light-chain, ... (7 entities in total)
Functional Keywordscoronavirus, spike, antibody, pdcov, pd41, complex, viral protein, structural genomics, center for structural genomics of infectious diseases, csgid
Biological sourcePorcine deltacoronavirus
More
Total number of polymer chains9
Total formula weight486501.46
Authors
Primary citationRexhepaj, 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-, 2024
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.6 Å)
Structure validation

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