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- PDB-9e21: CryoEM structure of a broadly neutralizing anti-SARS-CoV-2 antibody 52 -

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Basic information

Entry
Database: PDB / ID: 9.0E+21
TitleCryoEM structure of a broadly neutralizing anti-SARS-CoV-2 antibody 52
Components
  • 52 Fab Heavy chain
  • 52 Fab light chain
  • SARS XBB.1.5 Spike
KeywordsIMMUNE SYSTEM / SARS-CoV-2 / Antibody / RBD / Viral protein-immune system complex
Biological speciesHomo sapiens (human)
Severe acute respiratory syndrome coronavirus 2
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsJaiswal, D. / Bajic, G.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI168178 United States
CitationJournal: Sci Immunol / Year: 2025
Title: Germinal center-mediated broadening of B cell responses to SARS-CoV-2 booster immunization.
Authors: Sameer Kumar Malladi / Deepika Jaiswal / Baoling Ying / Wafaa B Alsoussi / Tamarand L Darling / Bernadeta Dadonaite / Alesandro Civljak / Stephen C Horvath / Julian Q Zhou / Wooseob Kim / ...Authors: Sameer Kumar Malladi / Deepika Jaiswal / Baoling Ying / Wafaa B Alsoussi / Tamarand L Darling / Bernadeta Dadonaite / Alesandro Civljak / Stephen C Horvath / Julian Q Zhou / Wooseob Kim / Jackson S Turner / Aaron J Schmitz / Fangjie Han / Suzanne M Scheaffer / Christopher W Farnsworth / Raffael Nachbagauer / Biliana Nestorova / Spyros Chalkias / Michael K Klebert / Darin K Edwards / Robert Paris / Benjamin S Strnad / William D Middleton / Jane A O'Halloran / Rachel M Presti / Jesse D Bloom / Adrianus C M Boon / Michael S Diamond / Goran Bajic / Ali H Ellebedy /
Abstract: Germinal centers (GCs) are key sites for antibody diversification and affinity maturation. SARS-CoV-2 messenger RNA (mRNA) vaccines elicit robust GC B cell responses in humans, but how these ...Germinal centers (GCs) are key sites for antibody diversification and affinity maturation. SARS-CoV-2 messenger RNA (mRNA) vaccines elicit robust GC B cell responses in humans, but how these responses influence the breadth of immunity against viral variants remains unclear. We analyzed GC B cell responses in nine healthy adults after mRNA booster immunization. We show that 77.8% of the B cell clones in the GC expressed representative monoclonal antibodies (mAbs) recognizing the spike protein, with 37.8% of these targeting the receptor binding domain (RBD). One RBD-targeting mAb, mAb-52, neutralized all tested SARS-CoV-2 strains, including the recent XEC variant. mAb-52 used the public clonotype, protected hamsters challenged against the EG.5.1 variant, and targeted the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Its broad reactivity was driven by extensive somatic hypermutation, underscoring the critical role of GC reactions in shaping cross-variant B cell immunity after SARS-CoV-2 booster vaccination.
History
DepositionOct 21, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 30, 2025Provider: repository / Type: Initial release
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: 52 Fab Heavy chain
L: 52 Fab light chain
S: SARS XBB.1.5 Spike
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,6814
Polymers46,4593
Non-polymers2211
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Antibody 52 Fab Heavy chain


Mass: 12572.168 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#2: Antibody 52 Fab light chain


Mass: 11220.589 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#3: Protein SARS XBB.1.5 Spike


Mass: 22666.639 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Production host: Homo sapiens (human)
#4: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H15NO6 / Feature type: SUBJECT OF INVESTIGATION
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: 52 Fab complex with RBD on XBB.1.5 spike / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES
Buffer solutionpH: 7.5
SpecimenConc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2300 nm / Nominal defocus min: 900 nm
Image recordingElectron dose: 48.95 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.21.2_5419 / Category: model refinement
CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 252670 / Symmetry type: POINT
RefinementHighest resolution: 3.1 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0023372
ELECTRON MICROSCOPYf_angle_d0.4644585
ELECTRON MICROSCOPYf_dihedral_angle_d4.093483
ELECTRON MICROSCOPYf_chiral_restr0.043498
ELECTRON MICROSCOPYf_plane_restr0.004592

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