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- EMDB-65803: Immune complex of P5-1C8 Fab binding the RBD of Omicron JN.1 6p s... -

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Entry
Database: EMDB / ID: EMD-65803
TitleImmune complex of P5-1C8 Fab binding the RBD of Omicron JN.1 6p spike protein
Map dataImmune complex of P5-1C8 Fab binding the RBD of Omicron JN.1 6p spike protein
Sample
  • Complex: SARS-CoV-2 WT 6p in complex with P5-1C8 IgG
    • Complex: Omicron JN.1 6p
    • Complex: P5-1C8 Fab
KeywordsSARS-CoV-2 / antibody / complex / RBD / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Homo sapiens (human)
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
AuthorsLv NN / Yang RY
Funding support2 items
OrganizationGrant numberCountry
Other government2022YFA1206400
Other governmentCIFMS 2019-I2M-5-018
CitationJournal: Adv Sci (Weinh) / Year: 2025
Title: IgG-Bridging-Seeded Synergistic Aggregation of SARS-CoV-2 Spikes Underlies Potent Neutralization by a Low-Affinity Antibody.
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 ...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 /
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.
History
DepositionAug 11, 2025-
Header (metadata) releaseJan 7, 2026-
Map releaseJan 7, 2026-
UpdateJan 7, 2026-
Current statusJan 7, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_65803.png

Downloads & links

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Map

FileDownload / File: emd_65803.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationImmune complex of P5-1C8 Fab binding the RBD of Omicron JN.1 6p spike protein
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.21 Å/pix.
x 192 pix.
= 424.32 Å		2.21 Å/pix.
x 192 pix.
= 424.32 Å		2.21 Å/pix.
x 192 pix.
= 424.32 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.21 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.016
Minimum - Maximum-0.0327777 - 0.09045415
Average (Standard dev.)0.00023191528 (±0.0047206124)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 424.32 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: Immune complex of P5-1C8 Fab binding the RBD...

Fileemd_65803_half_map_1.map
AnnotationImmune complex of P5-1C8 Fab binding the RBD of Omicron JN.1 6p spike protein
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Immune complex of P5-1C8 Fab binding the RBD...

Fileemd_65803_half_map_2.map
AnnotationImmune complex of P5-1C8 Fab binding the RBD of Omicron JN.1 6p spike protein
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : SARS-CoV-2 WT 6p in complex with P5-1C8 IgG

EntireName: SARS-CoV-2 WT 6p in complex with P5-1C8 IgG
Components
  • Complex: SARS-CoV-2 WT 6p in complex with P5-1C8 IgG
    • Complex: Omicron JN.1 6p
    • Complex: P5-1C8 Fab

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Supramolecule #1: SARS-CoV-2 WT 6p in complex with P5-1C8 IgG

SupramoleculeName: SARS-CoV-2 WT 6p in complex with P5-1C8 IgG / type: complex / ID: 1 / Parent: 0
Details: Immune complex of P5-1C8 IgG binding the RBD of SARS-CoV-2 WT 6p spike protein
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #2: Omicron JN.1 6p

SupramoleculeName: Omicron JN.1 6p / type: complex / ID: 2 / Parent: 1 / Details: Omicron JN.1 6p spike protein
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #3: P5-1C8 Fab

SupramoleculeName: P5-1C8 Fab / type: complex / ID: 3 / Parent: 1 / Details: P5-1C8 Fab
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
StainingType: NEGATIVE / Material: Uranyl Acetate

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Electron microscopy

MicroscopeJEOL 2100F
Image recordingFilm or detector model: OTHER / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.5 µm

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Image processing

CTF correctionSoftware - Name: Gctf / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

5x58

Final reconstructionResolution.type: BY AUTHOR / Resolution: 25.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION / Number images used: 11796
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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