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Yorodumi- PDB-6wxl: Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6wxl | ||||||
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Title | Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited, human antibody 1D12 in complex with an H7 SH13 HA trimer | ||||||
Components |
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Keywords | IMMUNE SYSTEM / VRC / VRC315 / Group 2 / Fab | ||||||
Function / homology | Function and homology information viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / host cell surface receptor binding / apical plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane Similarity search - Function | ||||||
Biological species | Influenza A virus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.76 Å | ||||||
Authors | Gorman, J. / Kwong, P.D. | ||||||
Funding support | United States, 1items
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Citation | Journal: Structure / Year: 2022 Title: Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite. Authors: Crystal Sao-Fong Cheung / Jason Gorman / Sarah F Andrews / Reda Rawi / Mateo Reveiz / Chen-Hsiang Shen / Yiran Wang / Darcy R Harris / Alexandra F Nazzari / Adam S Olia / Julie Raab / I-Ting ...Authors: Crystal Sao-Fong Cheung / Jason Gorman / Sarah F Andrews / Reda Rawi / Mateo Reveiz / Chen-Hsiang Shen / Yiran Wang / Darcy R Harris / Alexandra F Nazzari / Adam S Olia / Julie Raab / I-Ting Teng / Raffaello Verardi / Shuishu Wang / Yongping Yang / Gwo-Yu Chuang / Adrian B McDermott / Tongqing Zhou / Peter D Kwong / Abstract: Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, ...Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, 315-19-1D12. The cryo-EM structure of 315-19-1D12 Fab in complex with the hemagglutinin (HA) trimer revealed the antibody to recognize the helix A region of the HA stem, at the supersite of vulnerability recognized by group 1-specific and by cross-group-neutralizing antibodies. 315-19-1D12 was derived from HV1-2 and KV2-28 genes and appeared to form a new antibody class. Bioinformatic analysis indicated its group 2 neutralization specificity to be a consequence of four key residue positions. We specifically tested the impact of the group 1-specific N33 glycan, which decreased but did not abolish group 2 binding of 315-19-1D12. Overall, this study highlights the recognition of a broad group 2-neutralizing antibody, revealing unexpected diversity in neutralization specificity for antibodies that recognize the HA stem supersite. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6wxl.cif.gz | 382.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6wxl.ent.gz | 311.4 KB | Display | PDB format |
PDBx/mmJSON format | 6wxl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6wxl_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 6wxl_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6wxl_validation.xml.gz | 67.7 KB | Display | |
Data in CIF | 6wxl_validation.cif.gz | 98.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wx/6wxl ftp://data.pdbj.org/pub/pdb/validation_reports/wx/6wxl | HTTPS FTP |
-Related structure data
Related structure data | 21961MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 35039.473 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus (A/Shanghai/JS01/2013(H7N9)) Strain: A/Shanghai/JS01/2013(H7N9) / Gene: HA / Production host: Homo sapiens (human) / References: UniProt: A0A067Y6L0 #2: Protein | Mass: 25234.352 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus (A/Shanghai/JS01/2013(H7N9)) Strain: A/Shanghai/JS01/2013(H7N9) / Gene: HA / Production host: Homo sapiens (human) / References: UniProt: A0A067Y6L0 #3: Antibody | Mass: 23971.762 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Antibody | Mass: 25042.229 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #5: Sugar | ChemComp-NAG / Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Buffer component | Formula: PBS | ||||||||||||||||||||||||
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited, human antibody 1D12 in complex with an H7 SH13 HA trimer | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid type: C-flat-1.2/1.3 4C | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 293 K |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / C2 aperture diameter: 70 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 2 sec. / Electron dose: 49.9 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1878 |
Image scans | Movie frames/image: 50 |
-Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.76 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 142628 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building |
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Refine LS restraints |
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