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- EMDB-48550: SARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-48550
TitleSARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab
Map data
Sample
  • Complex: Structure of SARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab
    • Protein or peptide: NICA01A-1401 Fab Heavy chain
    • Protein or peptide: NICA01A-1401 Fab Light chain
    • Protein or peptide: Spike protein S2
KeywordsSARS-CoV-2 / Spike / S2 / COVID / monoclonal antibody / complex / Viral protein / Viral protein-immune system complex / VIRUS
Function / homology
Function and homology information


symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / viral translation / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion ...symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / viral translation / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / membrane fusion / entry receptor-mediated virion attachment to host cell / Attachment and Entry / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane
Similarity search - Function
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, N-terminal domain superfamily / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Spike glycoprotein, betacoronavirus / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, N-terminal domain superfamily / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Spike glycoprotein, betacoronavirus / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Biological speciesHomo sapiens (human) / Severe acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 3.79 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

Downloads & links

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Map

FileDownload / File: emd_48550.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 440 pix.
= 319. Å
0.73 Å/pix.
x 440 pix.
= 319. Å
0.73 Å/pix.
x 440 pix.
= 319. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.725 Å
Density
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.7188761 - 0.9364367
Average (Standard dev.)0.0002670079 (±0.008196025)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 319.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_48550_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_48550_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_48550_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 NICA01A-1401 Fab

EntireName: Structure of SARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab
Components
  • Complex: Structure of SARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab
    • Protein or peptide: NICA01A-1401 Fab Heavy chain
    • Protein or peptide: NICA01A-1401 Fab Light chain
    • Protein or peptide: Spike protein S2

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Supramolecule #1: Structure of SARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab

SupramoleculeName: Structure of SARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: NICA01A-1401 Fab Heavy chain

MacromoleculeName: NICA01A-1401 Fab Heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.621221 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYIHWVRQA PGQGLEWMGW INPNSDVTNY AQKFQGRVTM TRDTSISTAY MELSRLRSD DTAVYYCARE ATMIRGPSDF DYWGQGTLVT VSS

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Macromolecule #2: NICA01A-1401 Fab Light chain

MacromoleculeName: NICA01A-1401 Fab Light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.453561 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QSVLSQPPSV SGAPGQRVTI SCTGSSSNIG AGYDVHWYQQ LPGTAPKLLI YGNNNRPSGV PDRFSGSKSG TSASLAITGL QAEDEADYY CQSYDRSLSV VFGGGTKLTV L

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Macromolecule #3: Spike protein S2

MacromoleculeName: Spike protein S2 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 52.069832 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SLGAENSVAY SNNSIAIPTN FTISVTTEIL PVSMTKTSVD CTMYICGDST ECSNLLLQYG SFCTQLNRAL TGIAVEQDKN TQEVFAQVK QIYKTPPIKD FGGFNFSQIL PDPSKPSKRS PIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN G LTVLPPLL ...String:
SLGAENSVAY SNNSIAIPTN FTISVTTEIL PVSMTKTSVD CTMYICGDST ECSNLLLQYG SFCTQLNRAL TGIAVEQDKN TQEVFAQVK QIYKTPPIKD FGGFNFSQIL PDPSKPSKRS PIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN G LTVLPPLL TDEMIAQYTS ALLACTITSG WTCGAGPALQ IPFPMQMAYR FNGIGVPQNV LYENQKLIAN QFNSAIGKIQ DS LSSTPSA LGKLQDVVNQ NAQALNTLVK QLSSNFGAIS SVLNDILSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAE IRASAN LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGVVFL HVTYVPAQEK NFTTAPAICH DGKAHFPREG VFVS NGTHW FVTQRNFYEP QIITCDNTFV SGNCDVVIGI VNNTVYCPLQ PELDSFKEEL DKYFKNHTSG SHHHHHHHH

UniProtKB: Spike glycoprotein

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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: 3.79 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 115033
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:

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

PDB-9mr2:
SARS-CoV-2 S2 monomer in complex with NICA01A-1401 Fab

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