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Yorodumi- PDB-7m42: Complex of SARS-CoV-2 receptor binding domain with the Fab fragme... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7m42 | ||||||
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Title | Complex of SARS-CoV-2 receptor binding domain with the Fab fragments of neutralizing antibodies REGN10985 and REGN10989 | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-Cov-2 / RBD / neutralizing antibody / VIRAL PROTEIN-IMMUNE SYSTEM 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 / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Zhou, Y. / Romero Hernandez, A. / Saotome, K. / Franklin, M.C. | ||||||
Citation | Journal: Cell / Year: 2021 Title: The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies. Authors: Richard Copin / Alina Baum / Elzbieta Wloga / Kristen E Pascal / Stephanie Giordano / Benjamin O Fulton / Anbo Zhou / Nicole Negron / Kathryn Lanza / Newton Chan / Angel Coppola / Joyce Chiu ...Authors: Richard Copin / Alina Baum / Elzbieta Wloga / Kristen E Pascal / Stephanie Giordano / Benjamin O Fulton / Anbo Zhou / Nicole Negron / Kathryn Lanza / Newton Chan / Angel Coppola / Joyce Chiu / Min Ni / Yi Wei / Gurinder S Atwal / Annabel Romero Hernandez / Kei Saotome / Yi Zhou / Matthew C Franklin / Andrea T Hooper / Shane McCarthy / Sara Hamon / Jennifer D Hamilton / Hilary M Staples / Kendra Alfson / Ricardo Carrion / Shazia Ali / Thomas Norton / Selin Somersan-Karakaya / Sumathi Sivapalasingam / Gary A Herman / David M Weinreich / Leah Lipsich / Neil Stahl / Andrew J Murphy / George D Yancopoulos / Christos A Kyratsous / Abstract: Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight ...Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment-induced emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of virus variants in SARS-COV-2 isolates found in COVID-19 patients treated with the two-antibody combination REGEN-COV, as well as in preclinical in vitro studies using single, dual, or triple antibody combinations, and in hamster in vivo studies using REGEN-COV or single monoclonal antibody treatments. Our study demonstrates that the combination of non-competing antibodies in REGEN-COV provides protection against all current SARS-CoV-2 variants of concern/interest and also protects against emergence of new variants and their potential seeding into the population in a clinical setting. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7m42.cif.gz | 231 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7m42.ent.gz | 160.8 KB | Display | PDB format |
PDBx/mmJSON format | 7m42.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7m42_validation.pdf.gz | 821.5 KB | Display | wwPDB validaton report |
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Full document | 7m42_full_validation.pdf.gz | 829.9 KB | Display | |
Data in XML | 7m42_validation.xml.gz | 34.4 KB | Display | |
Data in CIF | 7m42_validation.cif.gz | 51.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m4/7m42 ftp://data.pdbj.org/pub/pdb/validation_reports/m4/7m42 | HTTPS FTP |
-Related structure data
Related structure data | 23662MC M: map data used to model this data 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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-Components
-Antibody , 4 types, 4 molecules ABCD
#1: Antibody | Mass: 22709.975 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) |
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#2: Antibody | Mass: 24815.834 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: 22895.180 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) |
#5: Antibody | Mass: 24857.811 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) |
-Protein / Sugars , 2 types, 2 molecules E
#3: Protein | Mass: 28437.902 Da / Num. of mol.: 1 / Fragment: receptor binding domain (UNP residues 319-541) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P0DTC2 |
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#6: 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 |
-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: Complex of SARS-CoV-2 receptor binding domain with the Fab fragments of neutralizing antibodies REGN10985 and REGN10989 Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Source (recombinant) | Organism: Cricetulus griseus (Chinese hamster) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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 |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 146054 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 56.34 Å2 | ||||||||||||||||||||||||
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