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- EMDB-64093: Structure of the SFTSV Gn head protein in complex with Nb261 and Nb318 -

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Basic information

Entry
Database: EMDB / ID: EMD-64093
TitleStructure of the SFTSV Gn head protein in complex with Nb261 and Nb318
Map data
Sample
  • Complex: Gn head protein in complex with Nb261 and Nb318
    • Protein or peptide: SFTSV Gn head
    • Protein or peptide: Nb261
    • Protein or peptide: Nb318
KeywordsSFTSV / nanobodies / complex / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex
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 speciesSevere fever with thrombocytopenia syndrome virus / Vicugna pacos (alpaca)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.62 Å
AuthorsLiang SJ / Lou ZY / Wu XL
Funding support China, 1 items
OrganizationGrant numberCountry
National Science Foundation (NSF, China) China
CitationJournal: Sci Transl Med / Year: 2025
Title: A rationally designed cocktail of nanobodies elicited by heterologous vaccination confers protection against SFTSV in preclinical models.
Authors: Xilin Wu / Linjing Zhu / Shengjian Liang / Zhen Chang / Yaxin Wang / Qingcui Zou / Zhili Xu / Doudou Zhang / Jiaqian Hu / Shengya Geng / Zhifeng Li / Wenkui Yu / Zhiliang Hu / Ming Chen / Ke ...Authors: Xilin Wu / Linjing Zhu / Shengjian Liang / Zhen Chang / Yaxin Wang / Qingcui Zou / Zhili Xu / Doudou Zhang / Jiaqian Hu / Shengya Geng / Zhifeng Li / Wenkui Yu / Zhiliang Hu / Ming Chen / Ke Cao / Bei Jia / Hongxia Wei / Rentian Cai / Junyi Long / Xiaoman Yang / Qiaojiang Yang / Zhanjing Yu / Lingen Shi / Binghong Xu / Yangwu Zheng / Shengrui Meng / Jiameng Cai / Guangfeng Zhou / Kerui Zhu / Yunbo Dou / Zhiyong Lou / Minghua Li / Yan Wu / Zhiwei Wu /
Abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne phlebovirus, poses a growing public health threat, with no approved vaccines or targeted therapies. Its genetic ...Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne phlebovirus, poses a growing public health threat, with no approved vaccines or targeted therapies. Its genetic diversity and rapid reassortment have hindered the development of broadly effective interventions. Here, we isolated and characterized broadly neutralizing camelid nanobodies generated by a heterologous immunization strategy. These nanobodies exhibited cross-subtype neutralization and conferred protection against disease in humanized and lethal murine models of SFTSV infection. Structural analysis revealed binding to distinct, nonoverlapping epitopes on the viral glycoprotein complex. A rationally designed cocktail leveraging this epitope diversity achieved complete viral inhibition through synergistic mechanisms. In both murine and immunocompetent ferret models, the cocktail enabled efficient viral clearance and full protection against lethal challenge. These results demonstrate the therapeutic potential of nanobody cocktails for SFTSV infection and establish a generalizable framework for nanobody-based countermeasures against genetically variable emerging viruses, including other members of the Bunyavirales order.
History
DepositionApr 9, 2025-
Header (metadata) releaseOct 29, 2025-
Map releaseOct 29, 2025-
UpdateSep 9, 2026-
Current statusSep 9, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_64093.png

Downloads & links

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Map

FileDownload / File: emd_64093.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.06 Å/pix.
x 256 pix.
= 270.08 Å		1.06 Å/pix.
x 256 pix.
= 270.08 Å		1.06 Å/pix.
x 256 pix.
= 270.08 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.055 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 4.0
Minimum - Maximum-0.058650114 - 13.878676
Average (Standard dev.)-0.006264481 (±0.2929831)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 270.08 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_64093_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_64093_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Gn head protein in complex with Nb261 and Nb318

EntireName: Gn head protein in complex with Nb261 and Nb318
Components
  • Complex: Gn head protein in complex with Nb261 and Nb318
    • Protein or peptide: SFTSV Gn head
    • Protein or peptide: Nb261
    • Protein or peptide: Nb318

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Supramolecule #1: Gn head protein in complex with Nb261 and Nb318

SupramoleculeName: Gn head protein in complex with Nb261 and Nb318 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Severe fever with thrombocytopenia syndrome virus

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Macromolecule #1: SFTSV Gn head

MacromoleculeName: SFTSV Gn head / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Severe fever with thrombocytopenia syndrome virus
Molecular weightTheoretical: 35.366055 KDa
Recombinant expressionOrganism: Homo (humans)
SequenceString: DSGPIICAGP IHSNKSADIP HLLGYSEKIC QIDRLIHVSS WLRNHSQFQG YVGQRGGRSQ VSYYPAENSY SRWSGLLSPC DADWLGMLV VKKAKGSDMI VPGPSYKGKV FFERPTFDGY VGWGCGSGKS RTESGELCSS DSGTSSGLLP SNRVLWIGDV A CQPMTPIP ...String:
DSGPIICAGP IHSNKSADIP HLLGYSEKIC QIDRLIHVSS WLRNHSQFQG YVGQRGGRSQ VSYYPAENSY SRWSGLLSPC DADWLGMLV VKKAKGSDMI VPGPSYKGKV FFERPTFDGY VGWGCGSGKS RTESGELCSS DSGTSSGLLP SNRVLWIGDV A CQPMTPIP EETFLELKSF SQSEFPDICK IDGIVFNQCE GESLPQPFDV AWMDVGHSHK IIMREHKTKW VQESSSKDFV CY KEGTGPC SESEEKTCKT SGSCRGDMQF CKVAGCEHGE EASEAKCRCS LVHKPGEVVV SYGGMRVRPK CYGFSRMMAT LEV N

UniProtKB: Envelopment polyprotein

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Macromolecule #2: Nb261

MacromoleculeName: Nb261 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Vicugna pacos (alpaca)
Molecular weightTheoretical: 12.681106 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
EVQLVESGGG LVQPGGSLRL SCAASGFTIS NADMRWYRQA PGKERELVAL LLSSLGGSTE YADSVKGRFT MFRDNARNTV YLQMDNLKA EDTAVYYCNV RWTDYWGQGT QVTVSS

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Macromolecule #3: Nb318

MacromoleculeName: Nb318 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Vicugna pacos (alpaca)
Molecular weightTheoretical: 13.363756 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
EVQLVESGGG LVQAGGSLRL SCTASGLTFS SYAMGWFRQA PGKEREFVAA ISWSGGDTYY EDSVKGRFTI SRDNAANTVY LQMNSLKPE DTAVYYCNSG GIATMKLMDQ YEYWGQGTQV TVSS

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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

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: DIFFRACTION / 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 AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.62 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 333824
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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