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- EMDB-67523: Epitope and functional classification of human neutralizing antib... -

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Basic information

Entry
Database: EMDB / ID: EMD-67523
TitleEpitope and functional classification of human neutralizing antibodies against SFTSV Gn
Map data
Sample
  • Complex: Gn-head/BD70-4003
    • Protein or peptide: BD70-4003 Heavy chain
    • Protein or peptide: BD70-4003 light chain
    • Protein or peptide: Glycoprotein N
KeywordsSFTSV / complex / VIRAL PROTEIN
Function / homology
Function and homology information


host cell Golgi membrane / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum membrane / fusion of virus membrane with host endosome membrane / symbiont entry into host cell / virion membrane / membrane
Similarity search - Function
Phlebovirus glycoprotein G1 / Phlebovirus glycoprotein G1 / Phlebovirus glycoprotein G2, fusion domain / Phlebovirus glycoprotein G2, C-terminal domain / Phlebovirus glycoprotein G2 fusion domain / Phlebovirus glycoprotein G2 C-terminal domain
Similarity search - Domain/homology
Envelopment polyprotein
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.85 Å
AuthorsWang QR / Jian FC / Wang YX
Funding support China, 1 items
OrganizationGrant numberCountry
Other government China
CitationJournal: Cell Rep / Year: 2026
Title: Human monoclonal antibodies that target the SFTSV glycoprotein Gn head from four neutralizing epitope groups.
Authors: Qianran Wang / Hao Li / Fanchong Jian / Aoxiang Han / Yuanni Liu / Jingyi Liu / Yuanling Yu / Jing Wang / Lingling Yu / Yanxia Wang / Haiyan Sun / Miaomiao Ma / Fei Shao / Liuluan Zhu / Wei Liu / Yunlong Cao /
Abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a lethal bunyavirus lacking approved countermeasures. From SFTS survivors, we isolate 84 human monoclonal antibodies (mAbs) against the ...Severe fever with thrombocytopenia syndrome virus (SFTSV) is a lethal bunyavirus lacking approved countermeasures. From SFTS survivors, we isolate 84 human monoclonal antibodies (mAbs) against the viral glycoproteins Gn and Gc. Gn-specific mAbs demonstrate superior neutralization breadth and potency compared to the restricted neutralizing activity observed with Gc. Using a high-throughput yeast display deep mutational scanning (DMS) platform, we classify Gn-head mAbs into eight epitope groups, among which four groups (IA, ID, IIIA, and IIIB) confer neutralization. Notably, mAbs BD70-4003 (group IA) and BD70-4017 (group IIIA) exhibit broad neutralization and provide 100% protection in a lethal mouse model. Cryo-electron microscopy (cryo-EM) structural analysis of these mAbs in complex with the Gn head reveals their binding interfaces, directly validating the epitope residues identified by DMS. Our study delineates the antigenic landscape of SFTSV Gn, identifies potent therapeutic candidates, and establishes DMS coupled with structural validation as a powerful framework for antibody discovery against bunyaviruses.
History
DepositionDec 5, 2025-
Header (metadata) releaseMay 6, 2026-
Map releaseMay 6, 2026-
UpdateMay 6, 2026-
Current statusMay 6, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_67523.png

Downloads & links

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Map

FileDownload / File: emd_67523.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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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

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.95 Å
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Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.162
Minimum - Maximum-1.6078149 - 2.4719512
Average (Standard dev.)-0.000022622711 (±0.042782895)
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_67523_msk_1.map
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Additional map: #1

Fileemd_67523_additional_1.map
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Half map: #2

Fileemd_67523_half_map_1.map
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Half map: #1

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Sample components

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Entire : Gn-head/BD70-4003

EntireName: Gn-head/BD70-4003
Components
  • Complex: Gn-head/BD70-4003
    • Protein or peptide: BD70-4003 Heavy chain
    • Protein or peptide: BD70-4003 light chain
    • Protein or peptide: Glycoprotein N

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Supramolecule #1: Gn-head/BD70-4003

SupramoleculeName: Gn-head/BD70-4003 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: BD70-4003 Heavy chain

MacromoleculeName: BD70-4003 Heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.898331 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
EVQLVQSGAE MKKPGESLKI SCQGSGYDFS IFWIGWVRQV PGKGLEWIGI IFPGDSNTRY NPSFQGQVTI SADESINTAY LQWSSLKSS DTAIYYCARH EDNGDYLTPY YVLDVWGQGT TVTVSS

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Macromolecule #2: BD70-4003 light chain

MacromoleculeName: BD70-4003 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.732007 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
DIQMTQSPSS QSASIGDTVT ITCRASDNIN NFLNWYQQKP GKAPKLMIYF ASHLQTGVPS RFSGSGSGTD FTLTISSLQP EDLATYYCQ QSFRTPSTFG QGTKIEIK

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Macromolecule #3: Glycoprotein N

MacromoleculeName: Glycoprotein N / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 35.320945 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DSGPIICAGP IHSNKSAGIP HLLGYSEKIC QIDRLIHVSS WLRNHSQFQG YVGQRGGRSQ VSYYPAENSY SRWSGLLSPC DADWLGMLV VKKAKESDMI VPGPSYKGKV FFERPTFDGY VGWGCGSGKS RTESGELCSS DSGTSSGLLP SDRVLWIGDV A CQPMTPIP ...String:
DSGPIICAGP IHSNKSAGIP HLLGYSEKIC QIDRLIHVSS WLRNHSQFQG YVGQRGGRSQ VSYYPAENSY SRWSGLLSPC DADWLGMLV VKKAKESDMI VPGPSYKGKV FFERPTFDGY VGWGCGSGKS RTESGELCSS DSGTSSGLLP SDRVLWIGDV A CQPMTPIP EETFLELKSF SQSEFPDICK IDGIVFNQCE GESLPQPFDV AWMDVGHSHK IIMREHKTKW VQESSSKDFV CY KEGTGPC SESEEKACKT SGSCRGDMQF CKVAGCEHGE EASEAKCRCS LVHKPGEVVV SYGGTRVRPK CYGFSRMMAT LEV N

UniProtKB: Envelopment polyprotein

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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
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.85 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 483639
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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