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- EMDB-65343: EBOV GP/1A10-VHH complex -

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Basic information

Entry
Database: EMDB / ID: EMD-65343
TitleEBOV GP/1A10-VHH complex
Map data
Sample
  • Complex: EBOV GP/1A10 complex
    • Protein or peptide: Envelope glycoprotein
    • Protein or peptide: Envelope glycoprotein,GP1
    • Protein or peptide: nanobody 1A10
Keywordsebolavirus / glycoprotein / Nanobody / Complex / MEMBRANE PROTEIN
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 / : / Filoviruses glycoprotein, extracellular domain / Filovirus glycoprotein / Envelope glycoprotein GP2-like, HR1-HR2
Similarity search - Domain/homology
Envelope glycoprotein / Envelope glycoprotein / Envelope glycoprotein
Similarity search - Component
Biological speciesZaire ebolavirus / Ebola virus - Gabon (1994-1997) / Vicugna pacos (alpaca)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.56 Å
AuthorsWang M / Gong P / Jin T
Funding support China, 3 items
OrganizationGrant numberCountry
Chinese Academy of SciencesXDB0490000 China
National Natural Science Foundation of China (NSFC)2022YFC2303300 China
National Natural Science Foundation of China (NSFC)82302522 China
CitationJournal: Nat Commun / Year: 2026
Title: A highly potent nanobody-based bispecific therapeutic provides broad-spectrum protection against ebolavirus.
Authors: Meihua Wang / Xinghai Zhang / Wujian Li / Yanfeng Yao / Entao Li / Baoyue Zhang / Jinge Zhou / Shunli Liu / Yongxiang Gao / Zhongliang Zhu / Lixia Zhu / Mengyao Liu / Jing Hu / Cheng Peng / ...Authors: Meihua Wang / Xinghai Zhang / Wujian Li / Yanfeng Yao / Entao Li / Baoyue Zhang / Jinge Zhou / Shunli Liu / Yongxiang Gao / Zhongliang Zhu / Lixia Zhu / Mengyao Liu / Jing Hu / Cheng Peng / Fangxu Li / Miaoyu Chen / Hang Liu / Chengbing Yao / Yuhua Shang / Feihu Yan / Peng Gong / Tengchuan Jin / Sandra Chiu /
Abstract: The highly lethal Ebola virus species-Zaire (EBOV), Sudan (SUDV), and Bundibugyo (BDBV)-pose persistent threats to global health. Current antibody therapies target EBOV but lack broad neutralization ...The highly lethal Ebola virus species-Zaire (EBOV), Sudan (SUDV), and Bundibugyo (BDBV)-pose persistent threats to global health. Current antibody therapies target EBOV but lack broad neutralization across ebolaviruses. Recent pan-ebolavirus strategies rely on antibody cocktails. Here, we identified two camelid-derived nanobodies (1A10 and BA2) that neutralize EBOV, SUDV, and BDBV in vitro and protect female rodents against these pathogens. High-resolution cryo-EM structures of their GP complexes showed that 1A10 and BA2 bind conserved but non-overlapping epitopes near the GP1 base and GP2's internal fusion loop (IFL), and biochemical analyses revealed their distinct neutralization mechanisms. To further improve efficacy, we engineered a bispecific antibody (BA2-1A10) via GS linker-mediated IgG-Fc fusion, which provided highly potent protection against all three viruses in female rodents model and positions it as a strong broad-spectrum anti-ebolavirus candidate. Our work demonstrates a structure-guided bispecific nanobody strategy for pan-ebolavirus therapy and highlights compact antibodies for next-generation antivirals.
History
DepositionJul 11, 2025-
Header (metadata) releaseJul 8, 2026-
Map releaseJul 8, 2026-
UpdateJul 8, 2026-
Current statusJul 8, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileReleased
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.95 Å/pix.
x 300 pix.
= 285. Å
0.95 Å/pix.
x 300 pix.
= 285. Å
0.95 Å/pix.
x 300 pix.
= 285. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.95 Å
Density
Contour LevelBy AUTHOR: 0.25
Minimum - Maximum-1.777755 - 2.6092699
Average (Standard dev.)-0.00043627524 (±0.047204845)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 285.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_65343_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_65343_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_65343_half_map_2.map
Projections & Slices
AxesZYX

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Sample components

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Entire : EBOV GP/1A10 complex

EntireName: EBOV GP/1A10 complex
Components
  • Complex: EBOV GP/1A10 complex
    • Protein or peptide: Envelope glycoprotein
    • Protein or peptide: Envelope glycoprotein,GP1
    • Protein or peptide: nanobody 1A10

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Supramolecule #1: EBOV GP/1A10 complex

SupramoleculeName: EBOV GP/1A10 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #2, #1, #3
Source (natural)Organism: Zaire ebolavirus

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Macromolecule #1: Envelope glycoprotein,GP1

MacromoleculeName: Envelope glycoprotein,GP1 / type: protein_or_peptide / ID: 1 / Details: mucin-deleted EBOV GP1,mucin-deleted EBOV GP1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Ebola virus - Gabon (1994-1997) / Strain: Gabon-94
Molecular weightTheoretical: 34.710973 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SIPLGVIHNS TLQVSDVDKL VCRDKLSSTN QLRSVGLNLE GNGVATDVPS ATKRWGFRSG VPPKVVNYEA GEWAENCYNL EIKKPDGSE CLPAAPDGIR GFPRCRYVHK VSGTGPCAGD FAFHKEGAFF LYDRLASTVI YRGTTFAEGV VAFLILPQAK K DFFSSHPL ...String:
SIPLGVIHNS TLQVSDVDKL VCRDKLSSTN QLRSVGLNLE GNGVATDVPS ATKRWGFRSG VPPKVVNYEA GEWAENCYNL EIKKPDGSE CLPAAPDGIR GFPRCRYVHK VSGTGPCAGD FAFHKEGAFF LYDRLASTVI YRGTTFAEGV VAFLILPQAK K DFFSSHPL REPVNATEDP SSGYYSTTIR YQATGFGTNE TEYLFEVDNL TYVQLESRFT PQFLLQLNET IYASGKRSNT TG KLIWKVN PEIDTTIGEW AFWETKKNLT RKIRSEELSF TAVSTGEESA SSGKLGLITN TIAGVAGLIT GGRRTRRP

UniProtKB: Envelope glycoprotein, Envelope glycoprotein

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Macromolecule #2: Envelope glycoprotein

MacromoleculeName: Envelope glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Zaire ebolavirus
Molecular weightTheoretical: 17.994176 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
REVIVNAQPK CNPNLHYWTT QDEGAAIGLA WIPYFGPAAE GIYTEGLMHN QNGLICGLRQ LANETTQALQ LFLRATTELR TFSILNRKA IDFLLQRWGG TCHILGPDCC IEPHDWTKNI TDKIDQIIHD FVDKTLPDQG DNDNWWTGWR QHHHHHH

UniProtKB: Envelope glycoprotein

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Macromolecule #3: nanobody 1A10

MacromoleculeName: nanobody 1A10 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Vicugna pacos (alpaca)
Molecular weightTheoretical: 14.73735 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QLQLVESGGG SVPSGGSLKL SCAASEYIYR RYCMGWFRQV PGKEREGVAA INSLGDTMYA DSVKGRFAIS QDSAKNTMYL HMNTLQPED TAVYYCAADA SYSPCYSAMT LRQSAYNSWG QGTQVTVSSH HHHHH

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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

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeJEOL CRYO ARM 300
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm

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Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.56 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 662790
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementProtocol: AB INITIO MODEL
Output model

PDB-9vts:
EBOV GP/1A10-VHH complex

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