8R9Y

S1B domain of the PDCoV spike glycoprotein in complex with the 67B12 and 42H3 antibody Fab fragments

Summary for 8R9Y

• Entry DOI: 10.2210/pdb8r9y/pdb
• EMDB information: 19016
• Descriptor: Spike protein, 67B12 antibody heavy chain, 67B12 antibody light chain, ... (7 entities in total)
• Functional Keywords: spike, coronavirus, antibody, complex, rbd, s1b, viral protein
• Biological source: Porcine deltacoronavirus; More
• Total number of polymer chains: 5
• Total formula weight: 116164.91

Authors

Debski-Antoniak, O.,Hurdiss, D.L. (deposition date: 2023-11-30, release date: 2024-06-05, Last modification date: 2024-10-23)

Primary citation

Du, W.,Debski-Antoniak, O.,Drabek, D.,van Haperen, R.,van Dortmondt, M.,van der Lee, J.,Drulyte, I.,van Kuppeveld, F.J.M.,Grosveld, F.,Hurdiss, D.L.,Bosch, B.J.
Neutralizing antibodies reveal cryptic vulnerabilities and interdomain crosstalk in the porcine deltacoronavirus spike protein.
Nat Commun, 15:5330-5330, 2024

PubMed Abstract: Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here, we generate and characterize a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to aminopeptidase N (APN), the entry receptor for PDCoV. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen.

PubMed: 38909062
DOI: 10.1038/s41467-024-49693-0

Experimental method

ELECTRON MICROSCOPY (3 Å)