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- EMDB-60113: SFTSV Gn in complex with JK-2/12 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-60113
TitleSFTSV Gn in complex with JK-2/12 Fab
Map data
Sample
  • Complex: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-2 and JK-12
KeywordsComplex / Neutralizing antibody / SFTSV / VIRAL PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.77 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_60113.png

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Map

FileDownload / File: emd_60113.map.gz / Format: CCP4 / Size: 193.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

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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

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.73 Å
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Contour LevelBy AUTHOR: 0.0189
Minimum - Maximum-0.28709224 - 0.62466323
Average (Standard dev.)-0.00023116087 (±0.00768154)
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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Mask #1

Fileemd_60113_msk_1.map
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Half map: #1

Fileemd_60113_half_map_1.map
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Half map: #2

Fileemd_60113_half_map_2.map
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Sample components

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Entire : Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-2...

EntireName: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-2 and JK-12
Components
  • Complex: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-2 and JK-12

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Supramolecule #1: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-2...

SupramoleculeName: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-2 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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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: 2.77 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 142314
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: ANGULAR RECONSTITUTION / Software - Name: cryoSPARC

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