9K6J
Crystal structure of SARS-CoV-2 WT RBD bound with P5-1C8 Fab
Summary for 9K6J
| Entry DOI | 10.2210/pdb9k6j/pdb |
| Descriptor | Spike protein S1, H chain of P5-1C8 Fab, L chain of P5-1C8 Fab, ... (5 entities in total) |
| Functional Keywords | crystal, sars-cov-2, rbd, antibody, viral protein/immune system, viral protein-immune system complex |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 3 |
| Total formula weight | 76908.93 |
| Authors | |
| Primary citation | Lv, N.,Chen, P.,Dai, X.,Xu, H.,Li, Z.,Shan, Z.,Li, J.,Guo, F.,Chen, Y.,Li, J.,Huang, Y.,Dong, G.,Jiang, Y.,Chen, L.,Nan, X.,Zhao, H.,Zhang, K.,Fan, S.,Dong, Y.,Liu, D.,Wang, X.,Huang, D.,Pan, X.,Chen, C.,Liu, Z.,Yan, L.T.,Zhang, Q.,Zhang, L.,Zhao, Y.,Yang, Y.R. IgG-Bridging-Seeded Synergistic Aggregation of SARS-CoV-2 Spikes Underlies Potent Neutralization by a Low-Affinity Antibody. Adv Sci, :e17192-e17192, 2025 Cited by PubMed Abstract: Mechanistic studies of viral neutralization typically prioritize high-affinity antibodies, relegating low-affinity binders to the sidelines. P5‑1C8, a Class 1 SARS-CoV-2 antibody that exemplifies this underexplored "low‑affinity yet high‑potency" phenotype is reported, retaining strong neutralization of Omicron JN.1 despite markedly weakened trimer binding (K = 225 nM; IC = 0.06 nM). Structural and biophysical analyses reveal that P5-1C8 engages WT and BA.1 spikes through canonical intra-spike bivalency, but with JN.1 it induces aggregation. Using virion-like nanoparticles displaying multiple spikes, it is shown that IgG remains bound with no detectable dissociation and triggers pronounced aggregation. Coarse-grained molecular dynamics delineate the stepwise pathway in which weak IgG-spike contacts seed aggregation via transient inter-spike bridging. Together, these findings establish the first mechanistic framework demonstrating how weak-binding antibodies can nonetheless achieve potent neutralization through higher-order aggregation, thereby expanding the conceptual landscape of antibody function and opening new directions for antibody evaluation and design. PubMed: 41355083DOI: 10.1002/advs.202517192 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.39 Å) |
Structure validation
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