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Yorodumi- PDB-7u8j: Crystal structure of chimeric hemagglutinin cH4/3 in complex with... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7u8j | ||||||
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Title | Crystal structure of chimeric hemagglutinin cH4/3 in complex with broad protective antibody 31.a.83 | ||||||
Components |
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Keywords | VIRAL PROTEIN/Immune System / Universal vaccine design / chimeric influenza hemagglutinin / HA trimer interface and stem / VIRAL PROTEIN-Immune System complex | ||||||
Function / homology | Function and homology information viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / membrane => GO:0016020 / 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 | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 4.9 Å | ||||||
Authors | Zhu, X. / Wilson, I.A. | ||||||
Funding support | United States, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Influenza chimeric hemagglutinin structures in complex with broadly protective antibodies to the stem and trimer interface. Authors: Xueyong Zhu / Julianna Han / Weina Sun / Eduard Puente-Massaguer / Wenli Yu / Peter Palese / Florian Krammer / Andrew B Ward / Ian A Wilson / Abstract: Influenza virus hemagglutinin (HA) has been the primary target for influenza vaccine development. Broadly protective antibodies targeting conserved regions of the HA unlock the possibility of ...Influenza virus hemagglutinin (HA) has been the primary target for influenza vaccine development. Broadly protective antibodies targeting conserved regions of the HA unlock the possibility of generating universal influenza immunity. Two group 2 influenza A chimeric HAs, cH4/3 and cH15/3, were previously designed to elicit antibodies to the conserved HA stem. Here, we show by X-ray crystallography and negative-stain electron microscopy that a broadly protective antistem antibody can stably bind to cH4/3 and cH15/3 HAs, thereby validating their potential as universal vaccine immunogens. Furthermore, flexibility was observed in the head domain of the chimeric HA structures, suggesting that antibodies could also potentially interact with the head interface epitope. Our structural and binding studies demonstrated that a broadly protective antihead trimeric interface antibody could indeed target the more open head domain of the cH15/3 HA trimer. Thus, in addition to inducing broadly protective antibodies against the conserved HA stem, chimeric HAs may also be able to elicit antibodies against the conserved trimer interface in the HA head domain, thereby increasing the vaccine efficacy. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7u8j.cif.gz | 172.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7u8j.ent.gz | 134.4 KB | Display | PDB format |
PDBx/mmJSON format | 7u8j.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7u8j_validation.pdf.gz | 422.3 KB | Display | wwPDB validaton report |
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Full document | 7u8j_full_validation.pdf.gz | 430.9 KB | Display | |
Data in XML | 7u8j_validation.xml.gz | 19.9 KB | Display | |
Data in CIF | 7u8j_validation.cif.gz | 29.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u8/7u8j ftp://data.pdbj.org/pub/pdb/validation_reports/u8/7u8j | HTTPS FTP |
-Related structure data
Related structure data | 7u8lC 7u8mC 4we8S 5kaqS 5xl1S S: Starting model for refinement 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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Unit cell |
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-Components
#1: Protein | Mass: 35731.094 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus / Production host: Trichoplusia ni (cabbage looper) |
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#2: Protein | Mass: 20453.730 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus / Gene: HA / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: A0A3B1ELE4 |
#3: Antibody | Mass: 23512.111 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster) |
#4: Antibody | Mass: 24894.752 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster) |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 4.38 Å3/Da / Density % sol: 71.91 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 0.1 M imidazole pH 8.0 and 10% (w/v) polyethylene glycol 8,000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 9, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 4.9→49.51 Å / Num. obs: 8670 / % possible obs: 99.7 % / Redundancy: 14.6 % / CC1/2: 0.996 / Rpim(I) all: 0.05 / Rsym value: 0.18 / Net I/σ(I): 15.3 |
Reflection shell | Resolution: 4.9→5.07 Å / Redundancy: 10.8 % / Mean I/σ(I) obs: 1 / Num. unique obs: 550 / CC1/2: 0.776 / Rpim(I) all: 0.3 / Rsym value: 1 / % possible all: 98.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5XL1,4WE8,5KAQ Resolution: 4.9→49.51 Å / SU ML: 0.75 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 43.11 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||
Displacement parameters | Biso max: 452.22 Å2 / Biso mean: 336.6011 Å2 / Biso min: 20 Å2 | ||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 4.9→49.51 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 3
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