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- EMDB-60112: SFTSV Gn in complex with JK-8/12 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-60112
TitleSFTSV Gn in complex with JK-8/12 Fab
Map data
Sample
  • Complex: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-8 and JK-12
    • Protein or peptide: JK-12 Fab light chain
    • Protein or peptide: JK-8 Fab light chain
    • Protein or peptide: JK-8 Fab heavy chain
    • Protein or peptide: JK-12 Fab heavy chain
    • Protein or peptide: Envelopment polyprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsComplex / Neutralizing antibody / SFTSV / VIRAL PROTEIN
Function / homology
Function and homology information


host cell Golgi membrane / host cell endoplasmic reticulum membrane / symbiont entry into host cell / fusion of virus membrane with host endosome membrane / 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: 2.37 Å
AuthorsShang H / Guo Y / Zhang N / Liu W / Li H
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: EBioMedicine / Year: 2025
Title: Discovery and characterization of potent broadly neutralizing antibodies from human survivors of severe fever with thrombocytopenia syndrome.
Authors: Shuo Zhang / Hang Shang / Shuo Han / Jiachen Li / Xuefang Peng / Yongxiang Wu / Xin Yang / Yu Leng / Fengze Wang / Ning Cui / Lingjie Xu / Hongkai Zhang / Yu Guo / Xiaoyu Xu / Nan Zhang / Wei Liu / Hao Li /
Abstract: BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne phlebovirus that causes viral hemorrhagic fever. Pandemic concerns have arisen due to the increased ...BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne phlebovirus that causes viral hemorrhagic fever. Pandemic concerns have arisen due to the increased human-to-human transmission and high mortality rate, highlighting the urgent need for specific therapeutics.
METHODS: Our observational study characterized the memory B cell response to natural SFTSV infection in four survivors. Monoclonal antibodies (mAbs) targeting the SFTSV glycoprotein N (Gn) were ...METHODS: Our observational study characterized the memory B cell response to natural SFTSV infection in four survivors. Monoclonal antibodies (mAbs) targeting the SFTSV glycoprotein N (Gn) were isolated and tested for in vitro neutralizing activities and effects on virus binding. Structural analysis was performed to identify neutralizing epitopes recognized by the mAbs. Prophylactical and therapeutical protections were evaluated using a lethal SFTSV infection model.
FINDINGS: The selected mAbs exhibiting neutralizing activity primarily originate from the IGHV5-51 and IGHV3-30 germlines and target four distinct antigenic sites on SFTSV Gn. These elite mAbs ...FINDINGS: The selected mAbs exhibiting neutralizing activity primarily originate from the IGHV5-51 and IGHV3-30 germlines and target four distinct antigenic sites on SFTSV Gn. These elite mAbs effectively blocked the interaction between Gn and the cell receptor, preventing infections from five phylogenetically distinct SFTSV clades. Structural analysis revealed a novel neutralizing epitope located within SFTSV Gn domain I recognized by the elite mAbs. In mice of lethal infections with different SFTSV strains, administering a low dose of elite mAbs significantly improved survival rates in both prophylactic and therapeutic settings.
INTERPRETATION: This study identifies potent broadly neutralizing antibodies that holds promise for use in humans against SFTSV infection and highlights inhibition of receptor binding as a crucial ...INTERPRETATION: This study identifies potent broadly neutralizing antibodies that holds promise for use in humans against SFTSV infection and highlights inhibition of receptor binding as a crucial mechanism for effective antibody-mediated neutralization against phleboviruses.
FUNDING: The National Key Research and Development Plan of China (2018YFE0200401, 2022YFC2303300), National Natural Science Foundation of China (81825019), China Postdoctoral Science Foundation (2023M741824).
History
DepositionMay 11, 2024-
Header (metadata) releaseJan 8, 2025-
Map releaseJan 8, 2025-
UpdateJan 8, 2025-
Current statusJan 8, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_60112.png

Downloads & links

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Map

FileDownload / File: emd_60112.map.gz / Format: CCP4 / Size: 193.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 370 pix.
= 270.1 Å		0.73 Å/pix.
x 370 pix.
= 270.1 Å		0.73 Å/pix.
x 370 pix.
= 270.1 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.73 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0263
Minimum - Maximum-0.24694641 - 0.5294916
Average (Standard dev.)-0.00025512392 (±0.0096631)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions370370370
Spacing370370370
CellA=B=C: 270.1 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_60112_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_60112_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 : Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-8...

EntireName: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-8 and JK-12
Components
  • Complex: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-8 and JK-12
    • Protein or peptide: JK-12 Fab light chain
    • Protein or peptide: JK-8 Fab light chain
    • Protein or peptide: JK-8 Fab heavy chain
    • Protein or peptide: JK-12 Fab heavy chain
    • Protein or peptide: Envelopment polyprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-8...

SupramoleculeName: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-8 and JK-12
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 150 KDa

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Macromolecule #1: JK-12 Fab light chain

MacromoleculeName: JK-12 Fab light chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.470803 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SELTQDPAVS VALGQTVRIT CQGDTLRRHY AAWYQQKPGQ APVLVIYDKN TRPSGIPDRF SGSSSGNTAS LTITGAQAED EADYYCNSR DSSDNLHVVF GGGTKLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK ...String:
SELTQDPAVS VALGQTVRIT CQGDTLRRHY AAWYQQKPGQ APVLVIYDKN TRPSGIPDRF SGSSSGNTAS LTITGAQAED EADYYCNSR DSSDNLHVVF GGGTKLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV AP

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Macromolecule #2: JK-8 Fab light chain

MacromoleculeName: JK-8 Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.067471 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPSS LSASVGDRVS ITCRASQTIS TYLNWYQQKP GRAPKLLIYG ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQ ESDSPSFTFG QGTKVQIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIQMTQSPSS LSASVGDRVS ITCRASQTIS TYLNWYQQKP GRAPKLLIYG ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQ ESDSPSFTFG QGTKVQIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRG

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Macromolecule #3: JK-8 Fab heavy chain

MacromoleculeName: JK-8 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.03175 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLVESGGG LVQPGGSLRL SCAASGIIVS DNYMSWVRQA PGKGLEWVSV IYTGGSTFYA DSVKGRFTIS RDRSKNTLDL QMNSLSAED TAVYYCARAL GAYDYAFDLW GQGNLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG ...String:
EVQLVESGGG LVQPGGSLRL SCAASGIIVS DNYMSWVRQA PGKGLEWVSV IYTGGSTFYA DSVKGRFTIS RDRSKNTLDL QMNSLSAED TAVYYCARAL GAYDYAFDLW GQGNLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS W NSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE P

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Macromolecule #4: JK-12 Fab heavy chain

MacromoleculeName: JK-12 Fab heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.544275 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLVQPGAE VKKPGESLKI SCKGSGYNFS NNWIGWVRQM PGKGLEYMGI IYPGDSDTRY NPSFKGQVTM SADRSISTAY LQWSSLKAS DTAIYYCARL YRRGWTTDAF DIWGQGTRVT ASSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String:
EVQLVQPGAE VKKPGESLKI SCKGSGYNFS NNWIGWVRQM PGKGLEYMGI IYPGDSDTRY NPSFKGQVTM SADRSISTAY LQWSSLKAS DTAIYYCARL YRRGWTTDAF DIWGQGTRVT ASSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HK

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Macromolecule #5: Envelopment polyprotein

MacromoleculeName: Envelopment polyprotein / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Severe fever with thrombocytopenia syndrome virus
Molecular weightTheoretical: 38.497418 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
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 NGLNDI FEAQKIEWHE AAAHHHHHHH H

UniProtKB: Envelopment polyprotein

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Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 1 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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: 7.2
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON III (4k 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: 2.4 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.37 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 400209
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: cryoSPARC

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