+Open data
-Basic information
Entry | Database: PDB / ID: 7m52 | ||||||
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Title | B6 Fab fragment bound to the HKU4 spike stem helix peptide | ||||||
Components |
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Keywords | ANTIVIRAL PROTEIN / IMMUNE SYSTEM / Broadly neutralizing antibody / Structural genomics / SSGCID / Center for Structural Genomics of Infectious Diseases / CSGID / Seattle Structural Genomics Center for Infectious Disease | ||||||
Function / homology | Function and homology information endocytosis involved in viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) Bat coronavirus HKU4 | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.5 Å | ||||||
Authors | Sauer, M.M. / Park, Y.J. / Veesler, D. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: Structural basis for broad coronavirus neutralization. Authors: Maximilian M Sauer / M Alejandra Tortorici / Young-Jun Park / Alexandra C Walls / Leah Homad / Oliver J Acton / John E Bowen / Chunyan Wang / Xiaoli Xiong / Willem de van der Schueren / Joel ...Authors: Maximilian M Sauer / M Alejandra Tortorici / Young-Jun Park / Alexandra C Walls / Leah Homad / Oliver J Acton / John E Bowen / Chunyan Wang / Xiaoli Xiong / Willem de van der Schueren / Joel Quispe / Benjamin G Hoffstrom / Berend-Jan Bosch / Andrew T McGuire / David Veesler / Abstract: Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying ...Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight β-coronavirus spike glycoproteins, including all five human-infecting β-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with β-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-β-coronavirus vaccine. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7m52.cif.gz | 208.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7m52.ent.gz | 163.6 KB | Display | PDB format |
PDBx/mmJSON format | 7m52.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m5/7m52 ftp://data.pdbj.org/pub/pdb/validation_reports/m5/7m52 | HTTPS FTP |
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-Related structure data
Related structure data | 7m51C 7m53C 7m55C 7m5eC 6nb8S S: Starting model for refinement 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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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein/peptide | Mass: 1849.986 Da / Num. of mol.: 1 / Fragment: Residues 1231-1245 of the spike glycoprotein / Source method: obtained synthetically / Source: (synth.) Bat coronavirus HKU4 / References: UniProt: A3EX94 | ||||
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#2: Antibody | Mass: 23348.107 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) | ||||
#3: Antibody | Mass: 24001.693 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) | ||||
#4: Chemical | #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.29 Å3/Da / Density % sol: 46.37 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 0.6 M Sodium Chloride, 0.1 M MES-NaOH, and 20% (w/v) PEG 4000 |
-Data collection
Diffraction | Mean temperature: 80 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 0.97741 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 R CdTe 300K / Detector: PIXEL / Date: Feb 7, 2020 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97741 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.42→46.69 Å / Num. obs: 80866 / % possible obs: 96.3 % / Redundancy: 3.4 % / Biso Wilson estimate: 17.85 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.056 / Rpim(I) all: 0.036 / Rrim(I) all: 0.067 / Net I/σ(I): 7.8 / Num. measured all: 277580 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement | ||||||
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Phasing MR |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6NB8 Resolution: 1.5→46.69 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 19.98 / 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: 75.26 Å2 / Biso mean: 26.7009 Å2 / Biso min: 8.75 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.5→46.69 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 26
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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