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Yorodumi- PDB-7m6d: Structure of the SARS-CoV-2 RBD in complex with neutralizing anti... -
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-Basic information
Entry | Database: PDB / ID: 7m6d | |||||||||
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Title | Structure of the SARS-CoV-2 RBD in complex with neutralizing antibodies BG4-25 and CR3022 | |||||||||
Components |
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Keywords | VIRAL PROTEIN/ANTIVIRAL PROTEIN / SARS-CoV-2 / Coronavirus / COVID-19 / antibody / neutralizing antibody / receptor binding domain / spike glycoprotein / ANTIVIRAL PROTEIN / VIRAL PROTEIN-ANTIVIRAL PROTEIN complex | |||||||||
Function / homology | Function and homology information Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.1 Å | |||||||||
Authors | Barnes, C.O. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell / Year: 2021 Title: B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV. Authors: Johannes F Scheid / Christopher O Barnes / Basak Eraslan / Andrew Hudak / Jennifer R Keeffe / Lisa A Cosimi / Eric M Brown / Frauke Muecksch / Yiska Weisblum / Shuting Zhang / Toni Delorey / ...Authors: Johannes F Scheid / Christopher O Barnes / Basak Eraslan / Andrew Hudak / Jennifer R Keeffe / Lisa A Cosimi / Eric M Brown / Frauke Muecksch / Yiska Weisblum / Shuting Zhang / Toni Delorey / Ann E Woolley / Fadi Ghantous / Sung-Moo Park / Devan Phillips / Betsabeh Tusi / Kathryn E Huey-Tubman / Alexander A Cohen / Priyanthi N P Gnanapragasam / Kara Rzasa / Theodora Hatziioanno / Michael A Durney / Xiebin Gu / Takuya Tada / Nathaniel R Landau / Anthony P West / Orit Rozenblatt-Rosen / Michael S Seaman / Lindsey R Baden / Daniel B Graham / Jacques Deguine / Paul D Bieniasz / Aviv Regev / Deborah Hung / Pamela J Bjorkman / Ramnik J Xavier / Abstract: Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell ...Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7m6d.cif.gz | 479 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7m6d.ent.gz | 349 KB | Display | PDB format |
PDBx/mmJSON format | 7m6d.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7m6d_validation.pdf.gz | 748.6 KB | Display | wwPDB validaton report |
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Full document | 7m6d_full_validation.pdf.gz | 767.1 KB | Display | |
Data in XML | 7m6d_validation.xml.gz | 39.5 KB | Display | |
Data in CIF | 7m6d_validation.cif.gz | 54.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m6/7m6d ftp://data.pdbj.org/pub/pdb/validation_reports/m6/7m6d | HTTPS FTP |
-Related structure data
Related structure data | 7m6eC 7m6fC 7m6gC 7m6hC 7m6iC 6w41S 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
-Antibody , 4 types, 4 molecules ABHL
#1: Antibody | Mass: 23800.793 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / Variant (production host): Expi293 |
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#2: Antibody | Mass: 24376.963 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / Variant (production host): Expi293 |
#4: Antibody | Mass: 23721.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / Variant (production host): Expi293 |
#5: Antibody | Mass: 23492.100 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / Variant (production host): Expi293 |
-Protein / Sugars , 2 types, 2 molecules C
#3: Protein | Mass: 24004.926 Da / Num. of mol.: 1 / Fragment: Receptor Binding Domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / Variant (production host): Expi293 / References: UniProt: P0DTC2 |
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#6: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.29 Å3/Da / Density % sol: 62.61 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / pH: 5 Details: 0.05 M citric acid, 0.05 M BIS-TRIS propane pH 5.0, 16% polyethylene glycol 3350 |
-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: 0.97946 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Nov 20, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 |
Reflection | Resolution: 3→38.79 Å / Num. obs: 31903 / % possible obs: 97.9 % / Redundancy: 6.1 % / Biso Wilson estimate: 73.5 Å2 / CC1/2: 0.972 / Rmerge(I) obs: 0.271 / Rpim(I) all: 0.125 / Net I/σ(I): 4 |
Reflection shell | Resolution: 3→3.16 Å / Rmerge(I) obs: 1.35 / Num. unique obs: 4079 / CC1/2: 0.259 / Rpim(I) all: 0.886 / % possible all: 88.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6W41 Resolution: 3.1→38.79 Å / SU ML: 0.4059 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 27.312 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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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 mean: 83.66 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.1→38.79 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 3.85838503712 Å / Origin y: -25.0656972438 Å / Origin z: -86.6102177919 Å
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Refinement TLS group | Selection details: all |