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

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Basic information

Entry
Database: PDB / ID: 9vts
TitleEBOV GP/1A10-VHH complex
Components
  • Envelope glycoprotein
  • Envelope glycoprotein,GP1
  • nanobody 1A10
KeywordsMEMBRANE PROTEIN / ebolavirus / glycoprotein / Nanobody / Complex
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
Vicugna pacos (alpaca)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.56 Å
AuthorsWang, M. / Gong, P. / Jin, T.
Funding support China, 3items
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, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 8, 2026Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Envelope glycoprotein,GP1
B: Envelope glycoprotein
G: nanobody 1A10
C: Envelope glycoprotein,GP1
D: Envelope glycoprotein
H: nanobody 1A10
E: Envelope glycoprotein,GP1
F: Envelope glycoprotein
I: nanobody 1A10
hetero molecules


Theoretical massNumber of molelcules
Total (without water)204,08712
Polymers202,3279
Non-polymers1,7603
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Envelope glycoprotein,GP1 / GP1 / 2


Mass: 34710.973 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Details: mucin-deleted EBOV GP1,mucin-deleted EBOV GP1
Source: (gene. exp.) Zaire ebolavirus, (gene. exp.) Ebola virus - Gabon (1994-1997)
Gene: GP / Strain: Gabon-94 / Production host: Homo sapiens (human) / References: UniProt: G8DB49, UniProt: O11457
#2: Protein Envelope glycoprotein / GP1 / 2


Mass: 17994.176 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Zaire ebolavirus / Gene: GP / Production host: Homo sapiens (human) / References: UniProt: A0A5J6EDK7
#3: Antibody nanobody 1A10


Mass: 14737.350 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Vicugna pacos (alpaca) / Production host: Homo sapiens (human)
#4: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}LINUCSPDB-CARE
Has ligand of interestN
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: EBOV GP/1A10 complex / Type: COMPLEX / Entity ID: #2, #1, #3 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Zaire ebolavirus186538
31Vicugna pacos (alpaca)30538
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

MicroscopyModel: JEOL CRYO ARM 300
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2PHENIX1.20.1_4487:model refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING ONLY
SymmetryPoint symmetry: C3 (3 fold cyclic)
3D reconstructionResolution: 2.56 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 662790 / Symmetry type: POINT
Atomic model buildingProtocol: AB INITIO MODEL
RefinementHighest resolution: 2.56 Å / Cross valid method: NONE
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0038577
ELECTRON MICROSCOPYf_angle_d0.52211661
ELECTRON MICROSCOPYf_dihedral_angle_d7.381251
ELECTRON MICROSCOPYf_chiral_restr0.0411320
ELECTRON MICROSCOPYf_plane_restr0.0061488

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