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- EMDB-48549: SARS-CoV-2 S2 monomer in complex with NICA01B-1113 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-48549
TitleSARS-CoV-2 S2 monomer in complex with NICA01B-1113 Fab
Map data
Sample
  • Complex: Structure of SARS-CoV-2 S2 monomer in complex with NICA01B-1113 Fab
KeywordsSARS-CoV-2 / Spike / S2 / COVID / monoclonal antibody / complex / Viral protein / Viral protein-immune system complex / VIRUS
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 5.7 Å
AuthorsPark S / Bangaru B / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-004923 United States
CitationJournal: J Exp Med / Year: 2025
Title: Common cold embecovirus imprinting primes broadly neutralizing antibody responses to SARS-CoV-2 S2.
Authors: Siriruk Changrob / Atsuhiro Yasuhara / Suncheol Park / Sandhya Bangaru / Lei Li / Chloe A Troxell / Peter J Halfmann / Steven A Erickson / Nicholas J Catanzaro / Meng Yuan / Panpan Zhou / ...Authors: Siriruk Changrob / Atsuhiro Yasuhara / Suncheol Park / Sandhya Bangaru / Lei Li / Chloe A Troxell / Peter J Halfmann / Steven A Erickson / Nicholas J Catanzaro / Meng Yuan / Panpan Zhou / Min Huang / G Dewey Wilbanks / Joshua J C McGrath / Gagandeep Singh / Sean A Nelson / Yanbin Fu / Nai-Ying Zheng / Sofia M Carayannopoulos / Haley L Dugan / Dustin G Shaw / Christopher T Stamper / Maria Lucia L Madariaga / Florian Krammer / Raiees Andrabi / Dennis R Burton / Andrew B Ward / Ian A Wilson / Yoshihiro Kawaoka / Patrick C Wilson /
Abstract: The S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is highly conserved across coronavirus strains and therefore is a potential pan-coronavirus vaccine target. ...The S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is highly conserved across coronavirus strains and therefore is a potential pan-coronavirus vaccine target. However, antibodies targeting this region are typically non-neutralizing. We report herein that S2-targeting antibodies from patients who recovered from SARS-CoV-2 infection bound only closely related sarbecovirus subgenus strains and, like most known S2 antibodies, none of these were neutralizing. In contrast, first-exposure, severe acutely infected COVID-19 patients predominantly induced back-boosted antibody-secreting cells imprinted against past common cold coronavirus strain OC43 that were cross-reactive to as many as five subgenera of betacoronavirus strains and gave rise to antibodies that were neutralizing and protective. The antibodies targeted two different sites: one defined by competition with stem helix antibodies, and the second to an underdescribed epitope at the apex of S2. These findings suggest that S2-targeted vaccines could strategically exploit controlled OC43 priming followed by SARS-CoV-2 boosting to enhance the breadth and quality of protective antibody responses.
History
DepositionJan 6, 2025-
Header (metadata) releaseNov 26, 2025-
Map releaseNov 26, 2025-
UpdateNov 26, 2025-
Current statusNov 26, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_48549.png

Downloads & links

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Map

FileDownload / File: emd_48549.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.72 Å/pix.
x 440 pix.
= 315.92 Å		0.72 Å/pix.
x 440 pix.
= 315.92 Å		0.72 Å/pix.
x 440 pix.
= 315.92 Å

Surface

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Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.718 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.05
Minimum - Maximum-0.13214976 - 0.2051528
Average (Standard dev.)0.000003792099 (±0.0051033627)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 315.91998 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_48549_msk_1.map
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AxesZYX

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Half map: #2

Fileemd_48549_half_map_1.map
Projections & Slices
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Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_48549_half_map_2.map
Projections & Slices
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Sample components

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Entire : Structure of SARS-CoV-2 S2 monomer in complex with NICA01B-1113 Fab

EntireName: Structure of SARS-CoV-2 S2 monomer in complex with NICA01B-1113 Fab
Components
  • Complex: Structure of SARS-CoV-2 S2 monomer in complex with NICA01B-1113 Fab

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Supramolecule #1: Structure of SARS-CoV-2 S2 monomer in complex with NICA01B-1113 Fab

SupramoleculeName: Structure of SARS-CoV-2 S2 monomer in complex with NICA01B-1113 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1 mg/mL
BufferpH: 8
Component:
ConcentrationFormulaName
20.0 mMTrisTris
150.0 mMNaClSodium Chloride
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 45.0 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: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 190000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN

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Image processing

CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 5.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 56153
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationSoftware - Name: cryoSPARC
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

6xr8


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL

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