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- EMDB-67541: Epitope and functional classification of human neutralizing antib... -

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Basic information

Entry
Database: EMDB / ID: EMD-67541
TitleEpitope and functional classification of human neutralizing antibodies against SFTSV Gn
Map data
Sample
  • Complex: Gn-head/BD70-4003
    • Protein or peptide: BD70-4017 heavy chain
    • Protein or peptide: BD70-4017 light chain
    • Protein or peptide: Envelopment polyprotein
  • Protein or peptide: BD70-4008 heavy chain
  • Protein or peptide: BD70-4008 light chain
KeywordsSFTSV / complex / VIRAL PROTEIN
Function / homology
Function and homology information


host cell Golgi membrane / host cell endoplasmic reticulum membrane / fusion of virus membrane with host endosome membrane / symbiont entry into host cell / virion attachment to 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) / Severe fever with thrombocytopenia syndrome virus
Methodsingle particle reconstruction / cryo EM / Resolution: 2.69 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) releaseApr 29, 2026-
Map releaseApr 29, 2026-
UpdateApr 29, 2026-
Current statusApr 29, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_67541.png

Downloads & links

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Map

FileDownload / File: emd_67541.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.95 Å/pix.
x 360 pix.
= 342. Å		0.95 Å/pix.
x 360 pix.
= 342. Å		0.95 Å/pix.
x 360 pix.
= 342. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.95 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.455
Minimum - Maximum-2.6591072 - 3.1868737
Average (Standard dev.)-0.00019668177 (±0.045585006)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 342.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_67541_msk_1.map
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Additional map: #1

Fileemd_67541_additional_1.map
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Half map: #2

Fileemd_67541_half_map_1.map
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Half map: #1

Fileemd_67541_half_map_2.map
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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: BD70-4017 heavy chain
    • Protein or peptide: BD70-4017 light chain
    • Protein or peptide: Envelopment polyprotein
  • Protein or peptide: BD70-4008 heavy chain
  • Protein or peptide: BD70-4008 light chain

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Supramolecule #1: Gn-head/BD70-4003

SupramoleculeName: Gn-head/BD70-4003 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: BD70-4017 heavy chain

MacromoleculeName: BD70-4017 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.738424 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EVQLVESGGG LVHPGGSLRL CCAATGFTSR TYWMNWVRQA PGKGLEWVAN MKQDGGETYY AGSVKGRFTI PRDDAENSLC LQMDNLRAE DTAVYYCARL RGWCYEGVCW GGFDLWGQGA LVTVSS

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Macromolecule #2: BD70-4017 light chain

MacromoleculeName: BD70-4017 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.42761 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QSVLTQPPSV SAAPGQRVTI SCSGNSSNMG VNYASWYQQL PGRAPTLLIY DNVKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYC GTWDSTLNAG VFGGGTKLTV L

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Macromolecule #3: Envelopment polyprotein

MacromoleculeName: Envelopment polyprotein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Severe fever with thrombocytopenia syndrome virus
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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Macromolecule #4: BD70-4008 heavy chain

MacromoleculeName: BD70-4008 heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.227812 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EVQLVESGGG LVKPGGSLRL SCAASGFTFS SYSMNWVRQA PGKGLEWVAS ISGSSAYIYY ADSMKGRFTI SRDNAKNSVY LQMNSLGVE DTAVYYCARD PASMLGDIGE LNHWGRGIRV TVSS

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Macromolecule #5: BD70-4008 light chain

MacromoleculeName: BD70-4008 light chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.541714 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
SYVLTQPPSV SVAPGNTARI TCGGDNIGSS AVHWYQQKPG QAPVVVLYDD SVRPSRIPER FSGSNSGNTA TLSISRVEAG DEADYYCQI WDTITSHRVF GGGTKLTVL

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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: 2.69 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 509899
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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