Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | IgG-Bridging-Seeded Synergistic Aggregation of SARS-CoV-2 Spikes Underlies Potent Neutralization by a Low-Affinity Antibody. |
|---|---|
| Journal, issue, pages | Adv Sci (Weinh), Page e17192, Year 2025 |
| Publish date | Dec 7, 2025 |
 Authors | Niannian Lv / Peng Chen / Xiaobin Dai / Hu Xu / Ziheng Li / Zelin Shan / Jinqian Li / Fenglin Guo / Yuanfang Chen / Jiayi Li / Yiqian Huang / Guizhi Dong / Yifan Jiang / Liang Chen / Xuanyu Nan / Hanjun Zhao / Kang Zhang / Shilong Fan / Yuanchen Dong / Dongsheng Liu / Xinquan Wang / Deli Huang / Xiaojing Pan / Chunying Chen / Zhihua Liu / Li-Tang Yan / Qi Zhang / Linqi Zhang / Yuliang Zhao / Yuhe Renee Yang /   |
| 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 ...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. |
 External links | Adv Sci (Weinh) / PubMed:41355083 |
| Methods | EM (single particle) / X-ray diffraction |
| Resolution | 2.39 - 25.0 Å |
| Structure data |  EMDB-65801: Cryo-EM structure of SARS-CoV-2 WT 6p spike protein in complex with P5-1C8 IgG (1.5 IgG)  EMDB-65802: Cryo-EM structure of SARS-CoV-2 WT 6p spike protein in complex with P5-1C8 IgG (1 IgG)  EMDB-65803: Immune complex of P5-1C8 Fab binding the RBD of Omicron JN.1 6p spike protein  EMDB-65804: Immune complex of P5-1C8 Fab binding the RBD of Omicron BA.1 6p spike protein (2 Fab)  EMDB-65805: Immune complex of P5-1C8 Fab binding the RBD of Omicron BA.1 6p spike protein (1 Fab)  EMDB-65806: Immune complex of P5-1C8 IgG binding the RBD of Omicron BA.1 6p spike protein  EMDB-65807: Immune complex of P5-1C8 Fab binding the RBD of SARS-CoV-2 WT 6p spike protein  EMDB-65808: Immune complex of P5-1C8 IgG binding the RBD of SARS-CoV-2 WT 6p spike protein  PDB-9k6j: |
| Chemicals |  ChemComp-NAG:  ChemComp-HOH: |
| Source |
|
 Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Crystal / SARS-CoV-2 / RBD / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex |
severe acute respiratory syndrome coronavirus 2
homo sapiens (human)