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Yorodumi- PDB-7mlz: Cryo-EM structure of SARS-CoV-2 spike in complex with neutralizin... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7mlz | ||||||
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Title | Cryo-EM structure of SARS-CoV-2 spike in complex with neutralizing antibody B1-182.1 that targets the receptor-binding domain | ||||||
Components |
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Keywords | IMMUNE SYSTEM/VIRAL PROTEIN / SARS-CoV-2 / receptor-binding domain / antibody / IMMUNE SYSTEM-VIRAL 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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / 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 | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.71 Å | ||||||
Authors | Zhou, T. / Tsybovsky, T. / Kwong, P.D. | ||||||
Funding support | United States, 1items
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Citation | Journal: Science / Year: 2021 Title: Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Authors: Lingshu Wang / Tongqing Zhou / Yi Zhang / Eun Sung Yang / Chaim A Schramm / Wei Shi / Amarendra Pegu / Olamide K Oloniniyi / Amy R Henry / Samuel Darko / Sandeep R Narpala / Christian ...Authors: Lingshu Wang / Tongqing Zhou / Yi Zhang / Eun Sung Yang / Chaim A Schramm / Wei Shi / Amarendra Pegu / Olamide K Oloniniyi / Amy R Henry / Samuel Darko / Sandeep R Narpala / Christian Hatcher / David R Martinez / Yaroslav Tsybovsky / Emily Phung / Olubukola M Abiona / Avan Antia / Evan M Cale / Lauren A Chang / Misook Choe / Kizzmekia S Corbett / Rachel L Davis / Anthony T DiPiazza / Ingelise J Gordon / Sabrina Helmold Hait / Tandile Hermanus / Prudence Kgagudi / Farida Laboune / Kwanyee Leung / Tracy Liu / Rosemarie D Mason / Alexandra F Nazzari / Laura Novik / Sarah O'Connell / Sijy O'Dell / Adam S Olia / Stephen D Schmidt / Tyler Stephens / Christopher D Stringham / Chloe Adrienna Talana / I-Ting Teng / Danielle A Wagner / Alicia T Widge / Baoshan Zhang / Mario Roederer / Julie E Ledgerwood / Tracy J Ruckwardt / Martin R Gaudinski / Penny L Moore / Nicole A Doria-Rose / Ralph S Baric / Barney S Graham / Adrian B McDermott / Daniel C Douek / Peter D Kwong / John R Mascola / Nancy J Sullivan / John Misasi / Abstract: The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. ...The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC) 0.3 to 11.1 nanograms per milliliter; IC 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development. | ||||||
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 | 7mlz.cif.gz | 118.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7mlz.ent.gz | 93.8 KB | Display | PDB format |
PDBx/mmJSON format | 7mlz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7mlz_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7mlz_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7mlz_validation.xml.gz | 37.1 KB | Display | |
Data in CIF | 7mlz_validation.cif.gz | 52.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ml/7mlz ftp://data.pdbj.org/pub/pdb/validation_reports/ml/7mlz | HTTPS FTP |
-Related structure data
Related structure data | 23914MC 7lrsC 7lrtC 7mm0C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 22100.756 Da / Num. of mol.: 1 / Fragment: Receptor binding domain, UNP residues 331-527 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
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#2: Antibody | Mass: 24285.312 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
#3: Antibody | Mass: 23536.008 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
#4: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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 |
Has ligand of interest | N |
-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: SARS-CoV-2 spike RBD in complex with neutralizing antibody B1-182.1 Type: COMPLEX Details: Local refinement of data collected for the complex made by mixing the SARS-CoV-2 spike protein and Fab fragment of antibody at a molar ratio of 1:3.6. Used particle substraction to obtain ...Details: Local refinement of data collected for the complex made by mixing the SARS-CoV-2 spike protein and Fab fragment of antibody at a molar ratio of 1:3.6. Used particle substraction to obtain RBD-Fab portion for refinement. Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.539951 MDa / Experimental value: NO |
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 / Details: 100 mM HEPES, 150 mM NaCl |
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Complex at 0.5 mg/mL concentration in the presence of 0.005% DDM |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277 K / Details: Blot for 4 seconds before plugging. |
-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 / Nominal magnification: 105000 X / Nominal defocus max: 2100 nm / Nominal defocus min: 1100 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: OTHER |
-Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.71 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 208776 Details: Local refinement with particles subtracted from SARS-CoV-2 spike-antibody complex. Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 7KLS | ||||||||||||||||||||||||
Refine LS restraints |
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