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Yorodumi- PDB-8tpa: H1 hemagglutinin (NC99) in complex with medial-junction-targeting... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8tpa | ||||||||||||
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Title | H1 hemagglutinin (NC99) in complex with medial-junction-targeting Fab 2-2-1G06 | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN/Immune System / influenza / hemagglutinin / monoclonal antibody / immune complex / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex | ||||||||||||
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: 3 Å | ||||||||||||
Authors | Yang, Y.R. / Han, J. / Perrett, H.R. / Ward, A.B. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: bioRxiv / Year: 2023 Title: Immune memory shapes human polyclonal antibody responses to H2N2 vaccination. Authors: Yuhe R Yang / Julianna Han / Hailee R Perrett / Sara T Richey / Abigail M Jackson / Alesandra J Rodriguez / Rebecca A Gillespie / Sarah O'Connell / Julie E Raab / Lauren Y Cominsky / Ankita ...Authors: Yuhe R Yang / Julianna Han / Hailee R Perrett / Sara T Richey / Abigail M Jackson / Alesandra J Rodriguez / Rebecca A Gillespie / Sarah O'Connell / Julie E Raab / Lauren Y Cominsky / Ankita Chopde / Masaru Kanekiyo / Katherine V Houser / Grace L Chen / Adrian B McDermott / Sarah F Andrews / Andrew B Ward / Abstract: Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase I clinical trial investigating a ferritin nanoparticle displaying H2 hemagglutinin in ...Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase I clinical trial investigating a ferritin nanoparticle displaying H2 hemagglutinin in H2-naïve and H2-exposed adults. Therefore, we could perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited after H2 vaccination. We temporally map the epitopes targeted by serum antibodies after first and second vaccinations and show previous H2 exposure results in higher responses to the variable head domain of hemagglutinin while initial responses in H2-naïve participants are dominated by antibodies targeting conserved epitopes. We use cryo-EM and monoclonal B cell isolation to describe the molecular details of cross-reactive antibodies targeting conserved epitopes on the hemagglutinin head including the receptor binding site and a new site of vulnerability deemed the medial junction. Our findings accentuate the impact of pre-existing influenza exposure on serum antibody responses. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8tpa.cif.gz | 427 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8tpa.ent.gz | 348.2 KB | Display | PDB format |
PDBx/mmJSON format | 8tpa.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8tpa_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 8tpa_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8tpa_validation.xml.gz | 72.6 KB | Display | |
Data in CIF | 8tpa_validation.cif.gz | 108.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tp/8tpa ftp://data.pdbj.org/pub/pdb/validation_reports/tp/8tpa | HTTPS FTP |
-Related structure data
Related structure data | 41471MC 8tp2C 8tp3C 8tp4C 8tp5C 8tp6C 8tp7C 8tp9C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Hemagglutinin ... , 2 types, 6 molecules ACGBFK
#1: Protein | Mass: 38289.207 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus (A/New Caledonia/20/1999(H1N1)) Gene: HA / Production host: Homo sapiens (human) / References: UniProt: Q6WG00 #4: Protein | Mass: 25065.277 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus (A/New Caledonia/20/1999(H1N1)) Gene: HA / Production host: Homo sapiens (human) / References: UniProt: Q6WG00 |
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-Antibody , 2 types, 6 molecules HDILEJ
#2: Antibody | Mass: 14020.630 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 11781.154 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 2 types, 15 molecules
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / |
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-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 | Name: H1 hemagglutinin (NC99) in complex with medial-junction-targeting Fab 2-2-1G06 Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Influenza A virus (A/New Caledonia/20/1999(H1N1)) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 48.6 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software | Name: Leginon / Category: image acquisition | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 124412 / Symmetry type: POINT | ||||||||||||||||||||||||
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