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- EMDB-44747: A broadly-neutralizing antibody against Ebolavirus glycoprotein t... -

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Basic information

Entry
Database: EMDB / ID: EMD-44747
TitleA broadly-neutralizing antibody against Ebolavirus glycoprotein that can potentiate the breadth and neutralization potency of other anti-glycoprotein antibodies
Map data
Sample
  • Complex: Zaire Ebola Glycoprotein dTM (GP1 and GP2 including MLD) complexed with 11883 and 11886
    • Complex: Zaire ebolavirus glycoprotein containing MLD
      • Protein or peptide: Virion spike glycoprotein GP1
      • Protein or peptide: Virion spike glycoprotein GP2
    • Complex: 11883 Fab heavy and light chains
      • Protein or peptide: 11883 heavy chain
      • Protein or peptide: 11883 light chain
    • Complex: 11886 Fab heavy and light chains
      • Protein or peptide: 11886 heavy chain
      • Protein or peptide: 11886 light chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsEbola / IgG / neutralization / complex / glycoprotein / VIRAL PROTEIN-IMMUNE SYSTEM complex / ebolavirus
Function / homology
Function and homology information


symbiont-mediated-mediated suppression of host tetherin activity / clathrin-dependent endocytosis of virus by host cell / entry receptor-mediated virion attachment to host cell / symbiont-mediated suppression of host innate immune response / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / host cell plasma membrane / virion membrane / extracellular region
Similarity search - Function
: / Filoviruses glycoprotein, extracellular domain / Filoviruses glycoprotein / Filovirus glycoprotein / Envelope glycoprotein GP2-like, HR1-HR2
Similarity search - Domain/homology
Envelope glycoprotein / Envelope glycoprotein
Similarity search - Component
Biological speciesEbola virus / Oryctolagus cuniculus (rabbit) / Ebolavirus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsDonnellan FR / Rayaprolu V / Rijal P / O'Dowd V / Parvate A / Callaway H / Hariharan C / Parekh D / Hui S / Shaffer K ...Donnellan FR / Rayaprolu V / Rijal P / O'Dowd V / Parvate A / Callaway H / Hariharan C / Parekh D / Hui S / Shaffer K / Hastie K / Shimanski L / Muller-Krauter H / Stecker T / Balaram A / Halfmann P / Saphire EO / Lightwood DJ / Townsend AR / Draper SJ
Funding support United Kingdom, 1 items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MR/N01796X/1 United Kingdom
CitationJournal: Npj Viruses / Year: 2026
Title: A broadly-neutralizing antibody against Orthoebolavirus glycoprotein that potentiates the breadth and neutralization of other antibodies.
Authors: Francesca R Donnellan / Vamseedhar Rayaprolu / Pramila Rijal / Victoria O'Dowd / Amar Parvate / Heather Callaway / Chitra Hariharan / Dipti Parekh / Sean Hui / Kelly C L Shaffer / Ruben Diaz ...Authors: Francesca R Donnellan / Vamseedhar Rayaprolu / Pramila Rijal / Victoria O'Dowd / Amar Parvate / Heather Callaway / Chitra Hariharan / Dipti Parekh / Sean Hui / Kelly C L Shaffer / Ruben Diaz Avalos / Kathryn M Hastie / Lisa Schimanski / Helena Müller-Kräuter / Thomas Strecker / Ariane Balaram / Peter Halfmann / Erica Ollmann Saphire / Daniel J Lightwood / Alain R Townsend / Simon J Draper /
Abstract: Ebolavirus disease (EVD) is caused by multiple species of orthoebolavirus. Monoclonal antibodies (mAbs) against the virus glycoprotein (GP) are the only class of therapeutic approved for treatment of ...Ebolavirus disease (EVD) is caused by multiple species of orthoebolavirus. Monoclonal antibodies (mAbs) against the virus glycoprotein (GP) are the only class of therapeutic approved for treatment of EVD caused by Orthoebolavirus zairense (Ebola virus, EBOV). Therefore, mAbs targeting multiple orthoebolavirus species may represent the next generation of EVD therapeutics. Broadly reactive anti-GP mAbs were produced; among these, mAbs 11886 and 11883 were broadly neutralizing in vitro. A 3.0 Å cryo-electron microscopy structure of EBOV GP bound to both mAbs shows that 11886 binds a novel epitope bridging the glycan cap (GC), 3 pocket and GP2 N-terminus, whereas 11883 binds the receptor binding region (RBR) and GC. In vitro, 11886 synergized with a range of mAbs with epitope specificities spanning the RBR/GC, including 11883. Notably, 11886 increased the breadth of neutralization by partner mAbs against different orthoebolavirus species. These data provide a strategic route to design improved mAb-based next-generation EVD therapeutics.
History
DepositionMay 5, 2024-
Header (metadata) releaseNov 5, 2025-
Map releaseNov 5, 2025-
UpdateMay 20, 2026-
Current statusMay 20, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_44747.png

Downloads & links

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Map

FileDownload / File: emd_44747.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.67 Å/pix.
x 512 pix.
= 340.787 Å		0.67 Å/pix.
x 512 pix.
= 340.787 Å		0.67 Å/pix.
x 512 pix.
= 340.787 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.6656 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.055
Minimum - Maximum-0.17135307 - 0.35193503
Average (Standard dev.)0.000084950516 (±0.009169778)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 340.7872 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_44747_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_44747_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Zaire Ebola Glycoprotein dTM (GP1 and GP2 including MLD) complexe...

EntireName: Zaire Ebola Glycoprotein dTM (GP1 and GP2 including MLD) complexed with 11883 and 11886
Components
  • Complex: Zaire Ebola Glycoprotein dTM (GP1 and GP2 including MLD) complexed with 11883 and 11886
    • Complex: Zaire ebolavirus glycoprotein containing MLD
      • Protein or peptide: Virion spike glycoprotein GP1
      • Protein or peptide: Virion spike glycoprotein GP2
    • Complex: 11883 Fab heavy and light chains
      • Protein or peptide: 11883 heavy chain
      • Protein or peptide: 11883 light chain
    • Complex: 11886 Fab heavy and light chains
      • Protein or peptide: 11886 heavy chain
      • Protein or peptide: 11886 light chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Zaire Ebola Glycoprotein dTM (GP1 and GP2 including MLD) complexe...

SupramoleculeName: Zaire Ebola Glycoprotein dTM (GP1 and GP2 including MLD) complexed with 11883 and 11886
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Molecular weightTheoretical: 450 KDa

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Supramolecule #2: Zaire ebolavirus glycoprotein containing MLD

SupramoleculeName: Zaire ebolavirus glycoprotein containing MLD / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #5-#6
Source (natural)Organism: Ebola virus
Molecular weightTheoretical: 180 KDa

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Supramolecule #3: 11883 Fab heavy and light chains

SupramoleculeName: 11883 Fab heavy and light chains / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 100 KDa

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Supramolecule #4: 11886 Fab heavy and light chains

SupramoleculeName: 11886 Fab heavy and light chains / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3-#4
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 100 KDa

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Macromolecule #1: 11883 heavy chain

MacromoleculeName: 11883 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Oryctolagus cuniculus (rabbit) / Organ: Spleen / Cell: Splenocytes
Molecular weightTheoretical: 15.837846 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
SFEATMETGL RWLLLVAVLK GVQCQEQLVE SGGGLVQPEG SLTLTCTASG FSFSSNCWRC WVRQAPGKGL EWIACVCAGR SGGTTYYAS WAKGRFTISK TSSPTVTLQM TSLTAADTAT YFCARAGYDD YGDASFFNLW GPGTLVTVS

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Macromolecule #2: 11883 light chain

MacromoleculeName: 11883 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 14.97094 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
SFEATMNMRA PTQLLGLLLL WLPGARCAVV LTQTASPVST PVGGTVTIKC QASQNIYSNL AWYQQKPGQP PKLLIYSAST LASGVPSRF KGSGSGTEYT LTISDLECAD AATYYCQRYY YLSGSADNTF GGGTEVVVKR T

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Macromolecule #3: 11886 heavy chain

MacromoleculeName: 11886 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 15.854976 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
RSFEATMETG LRWLLLVAVL KGVQCQSVEE SGGRLVTPGT PLTLTCIVSG FSLSNYYMSW VRQVPGKGLE WIGVIGWSGT SSYASWAKG RFTISKTAST TVDLKITSPT TEDTATYFCA RVLYIGGGFN YYDAFDPWGP GTLVTVS

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Macromolecule #4: 11886 light chain

MacromoleculeName: 11886 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 15.134112 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
RSFEATMNMR APTQLLGLLL LWLPGARCDV VMTQTPASVS EPVGGTVTIK CQASQSIGSN LAWYQQKPGQ PPKLLIYAAS TLASGVPSR FKGSGSGTEF TLTISDLECA DAATYYCQCT YYDSSYVYNN FGGGTEVVVK RT

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Macromolecule #5: Virion spike glycoprotein GP1

MacromoleculeName: Virion spike glycoprotein GP1 / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Ebolavirus
Molecular weightTheoretical: 31.256092 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: RSIPLGVIHN STLQVSDVDK LVCRDKLSST NQLRSVGLNL EGNGVATDVP SATKRWGFRS GVPPKVVNYE AGEWAENCYN LEIKKPDGS ECLPAAPDGI RGFPRCRYVH KVSGTGPCAG DFAFHKEGAF FLYDRLASTV IYRGTTFAEG VVAFLILPQA K KDFFSSHP ...String:
RSIPLGVIHN STLQVSDVDK LVCRDKLSST NQLRSVGLNL EGNGVATDVP SATKRWGFRS GVPPKVVNYE AGEWAENCYN LEIKKPDGS ECLPAAPDGI RGFPRCRYVH KVSGTGPCAG DFAFHKEGAF FLYDRLASTV IYRGTTFAEG VVAFLILPQA K KDFFSSHP LREPVNATED PSSGYYSTTI RYQATGFGTN ETEYLFEVDN LTYVQLESRF TPQFLLQLNE TIYTSGKRSN TT GKLIWKV NPEIDTTIGE WAFWETKKNL TRKIRSEELS FT

UniProtKB: Envelope glycoprotein

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Macromolecule #6: Virion spike glycoprotein GP2

MacromoleculeName: Virion spike glycoprotein GP2 / type: protein_or_peptide / ID: 6 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Ebolavirus
Molecular weightTheoretical: 15.206248 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString:
AIVNAQPKCN PNLHYWTTQD EGAAIGLAWI PYFGPAAEGI YTEGLMHNQD GLICGLRQLA NETTQALQLF LRATTELRTF SILNRKAID FLLQRWGGTC HILGPDCCIE PHDWTKNITD KIDQIIHDFV DKTLPD

UniProtKB: Envelope glycoprotein

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Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 9 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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

Concentration1.9 mg/mL
BufferpH: 7.5
Component:
ConcentrationNameFormula
50.0 mMTris
150.0 mMsodium chlorideNaCl
20.0 uMLMNG
GridModel: C-flat-2/1 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 35 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: GIF Bioquantum
DetailsTotal dose of 50e/A2
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 9552 / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 75000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

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

7tn9

Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 66500
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementProtocol: AB INITIO MODEL
Output model

PDB-9bop:
A broadly-neutralizing antibody against Ebolavirus glycoprotein that can potentiate the breadth and neutralization potency of other anti-glycoprotein antibodies

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