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Open data
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Basic information
Entry | Database: PDB / ID: 8zhq | ||||||
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Title | SFTSV Gn in complex with JK-8/12 Fab | ||||||
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![]() | VIRAL PROTEIN / Complex / Neutralizing antibody / SFTSV | ||||||
Function / homology | ![]() 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 | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.37 Å | ||||||
![]() | Shang, H. / Guo, Y. / Zhang, N. / Liu, W. / Li, H. | ||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 236 KB | Display | ![]() |
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PDB format | ![]() | 184.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 60112MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 1 types, 1 molecules E
#5: Protein | Mass: 38497.418 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() ![]() |
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-Antibody , 4 types, 4 molecules ABCD
#1: Antibody | Mass: 22470.803 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Antibody | Mass: 23067.471 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Antibody | Mass: 23031.750 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#4: Antibody | Mass: 22544.275 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 3 types, 3 molecules 
#6: Polysaccharide | alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#7: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#8: Sugar | ChemComp-NAG / |
-Details
Has ligand of interest | N |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Ternary complex of SFTSV Gn with neutralizing antibodies Fab JK-8 and JK-12 Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Molecular weight | Value: 0.15 MDa / Experimental value: YES |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.37 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 400209 / Symmetry type: POINT | ||||||||||||||||||||||||
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