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Yorodumi- PDB-8ct6: 1F8 mAb in complex with the computationally optimized broadly rea... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ct6 | ||||||
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Title | 1F8 mAb in complex with the computationally optimized broadly reactive H1 influenza hemagglutinin P1 | ||||||
Components |
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Keywords | Viral Protein/IMMUNE SYSTEM / Hemagglutinin / influenza virus / COBRA / monoclonal antibody / IMMUNE SYSTEM / Viral Protein-IMMUNE SYSTEM complex | ||||||
Biological species | Influenza A virus Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
Authors | Dzimianski, J.V. / DuBois, R.M. | ||||||
Funding support | United States, 1items
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Citation | Journal: Commun Biol / Year: 2023 Title: Structural insights into the broad protection against H1 influenza viruses by a computationally optimized hemagglutinin vaccine. Authors: John V Dzimianski / Julianna Han / Giuseppe A Sautto / Sara M O'Rourke / Joseph M Cruz / Spencer R Pierce / Jeffrey W Ecker / Michael A Carlock / Kaito A Nagashima / Jarrod J Mousa / Ted M ...Authors: John V Dzimianski / Julianna Han / Giuseppe A Sautto / Sara M O'Rourke / Joseph M Cruz / Spencer R Pierce / Jeffrey W Ecker / Michael A Carlock / Kaito A Nagashima / Jarrod J Mousa / Ted M Ross / Andrew B Ward / Rebecca M DuBois / Abstract: Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally ...Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins is a promising vaccine strategy to protect against a wide range of current and future influenza viruses. Though effective in preclinical studies, the mechanistic basis driving the broad reactivity of COBRA proteins remains to be elucidated. Here, we report the crystal structure of the COBRA HA termed P1 and identify antigenic and glycosylation properties that contribute to its immunogenicity. We further report the cryo-EM structure of the P1-elicited broadly neutralizing antibody 1F8 bound to COBRA P1, revealing 1F8 to recognize an atypical receptor binding site epitope via an unexpected mode of binding. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ct6.cif.gz | 413.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ct6.ent.gz | 307.1 KB | Display | PDB format |
PDBx/mmJSON format | 8ct6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ct6_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8ct6_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8ct6_validation.xml.gz | 68.5 KB | Display | |
Data in CIF | 8ct6_validation.cif.gz | 100 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ct/8ct6 ftp://data.pdbj.org/pub/pdb/validation_reports/ct/8ct6 | HTTPS FTP |
-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 3 molecules BAC
#1: Protein | Mass: 63264.535 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
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-Antibody , 2 types, 4 molecules LKHJ
#2: Antibody | Mass: 23918.271 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): CHO-S / Production host: Cricetulus griseus (Chinese hamster) #3: Antibody | Mass: 23900.818 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): CHO-S / Production host: Cricetulus griseus (Chinese hamster) |
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-Sugars , 4 types, 14 molecules
#4: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-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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#5: 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 | ||
#6: Polysaccharide | #7: Sugar | ChemComp-NAG / |
-Details
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
Component |
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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 / Details: TBS | ||||||||||||||||||||||||||||
Specimen | Conc.: 0.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: 1:3:3 molar ratio of P1 HA, 1F8, and P1-05 | ||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % |
-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 / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Image recording | Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 57151 / Symmetry type: POINT | |||||||||
Refinement | Cross valid method: NONE |