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- EMDB-62650: A35 of MPXV in complex with mAb975 -

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Basic information

Entry
Database: EMDB / ID: EMD-62650
TitleA35 of MPXV in complex with mAb975
Map data
Sample
  • Complex: A35 of MPXV in complex with mAb975
    • Protein or peptide: mab975HC
    • Protein or peptide: mab975KC
  • Protein or peptide: Protein OPG161
Keywordsenvelope glycoprotein / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homologyChordopoxvirus A33R / Chordopoxvirus A33R protein / C-type lectin-like/link domain superfamily / C-type lectin fold / host cell membrane / virion membrane / membrane / Protein OPG161
Function and homology information
Biological speciesHomo sapiens (human) / Monkeypox virus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsYan RH / Yang HN
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell / Year: 2025
Title: Structurally conserved human anti-A35 antibodies protect mice and macaques from mpox virus infection.
Authors: Bin Ju / Congcong Liu / Jingjing Zhang / Yaning Li / Haonan Yang / Bing Zhou / Baoying Huang / Jianrong Ma / Jiahan Lu / Lin Cheng / Zhe Cong / Lin Zhu / Tianhao Shi / Yuehong Sun / Na Li / ...Authors: Bin Ju / Congcong Liu / Jingjing Zhang / Yaning Li / Haonan Yang / Bing Zhou / Baoying Huang / Jianrong Ma / Jiahan Lu / Lin Cheng / Zhe Cong / Lin Zhu / Tianhao Shi / Yuehong Sun / Na Li / Ting Chen / Miao Wang / Shilong Tang / Xiangyang Ge / Juanjuan Zhao / Wen-Jie Tan / Renhong Yan / Jing Xue / Zheng Zhang /
Abstract: The A35 protein, expressed on the enveloped virion of monkeypox (mpox) virus (MPXV), is essential for viral infection and spread within the host, making it an effective antiviral target. In this ...The A35 protein, expressed on the enveloped virion of monkeypox (mpox) virus (MPXV), is essential for viral infection and spread within the host, making it an effective antiviral target. In this study, we demonstrated two human anti-A35 monoclonal antibodies (mAbs) displayed potential protection against MPXV in CAST/EiJ mice and rhesus macaques. Using cryo-electron microscopy, we determined two high-resolution structures of the A35 dimer in complex with the fragment of antigen binding of mAb 975 or mAb 981, revealing detailed interactions at the antigen-antibody interfaces. Structural analysis showed that these structurally conserved mAbs bind to a groove region at the interface of A35 dimer. Overall, we provided a proof of concept for a single administration of anti-A35 mAbs mitigating the pathogenic effects of MPXV infection in rhesus macaques. These human-derived mAbs could be served as antibody drug candidates, and their binding models to the A35 dimer will provide valuable insights for future vaccine design.
History
DepositionDec 9, 2024-
Header (metadata) releaseAug 13, 2025-
Map releaseAug 13, 2025-
UpdateDec 24, 2025-
Current statusDec 24, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_62650.png

Downloads & links

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Map

FileDownload / File: emd_62650.map.gz / Format: CCP4 / Size: 125 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.)
0.83 Å/pix.
x 320 pix.
= 264.64 Å		0.83 Å/pix.
x 320 pix.
= 264.64 Å		0.83 Å/pix.
x 320 pix.
= 264.64 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.827 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-0.22021505 - 0.8347716
Average (Standard dev.)0.0016647483 (±0.024092654)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 264.64 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_62650_half_map_1.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Half map: #1

Fileemd_62650_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram

Histogram (log scale)

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Sample components

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Entire : A35 of MPXV in complex with mAb975

EntireName: A35 of MPXV in complex with mAb975
Components
  • Complex: A35 of MPXV in complex with mAb975
    • Protein or peptide: mab975HC
    • Protein or peptide: mab975KC
  • Protein or peptide: Protein OPG161

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Supramolecule #1: A35 of MPXV in complex with mAb975

SupramoleculeName: A35 of MPXV in complex with mAb975 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #2-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Protein OPG161

MacromoleculeName: Protein OPG161 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Monkeypox virus
Molecular weightTheoretical: 9.261993 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
CNGLYYQGSC YILHSDYKSF EDAKANCAAE SSTLPNKSDV LTTWLIDYVE DTWGSDGNPI TKTTSDYQDS DVSQEVRKYF CT

UniProtKB: Protein OPG161

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Macromolecule #2: mab975HC

MacromoleculeName: mab975HC / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.109636 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
VQLQESGPGL VKPSGTLSLT CAVSRASISS SNWWSWLRQP PGKGLEWIGE IFHSGSTNYN PSLRSRVTIS VDKSKNQFSL NVSSVTAAD TAVYYCARSQ GGSGLFRAKW FDPWGQGTLV TV

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Macromolecule #3: mab975KC

MacromoleculeName: mab975KC / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.298476 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQHK PGQAPRLLMY GASSRAPGTP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYGSSPRTF GQGTKV

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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: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / 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 / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8xa4

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 180429
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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