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Yorodumi- PDB-7uow: SARS-Cov2 S protein structure in complex with neutralizing monocl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7uow | ||||||
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Title | SARS-Cov2 S protein structure in complex with neutralizing monoclonal antibody 034_32 | ||||||
Components |
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Keywords | VIRAL PROTEIN / SARS-Cov2 6P spike protein / immune 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 | Severe acute respiratory syndrome coronavirus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å | ||||||
Authors | Patel, A. / Ortlund, E. | ||||||
Funding support | United States, 1items
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Citation | Journal: Structure / Year: 2023 Title: Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response. Authors: Anamika Patel / Sanjeev Kumar / Lilin Lai / Chennareddy Chakravarthy / Rajesh Valanparambil / Elluri Seetharami Reddy / Kamalvishnu Gottimukkala / Prashant Bajpai / Dinesh Ravindra Raju / ...Authors: Anamika Patel / Sanjeev Kumar / Lilin Lai / Chennareddy Chakravarthy / Rajesh Valanparambil / Elluri Seetharami Reddy / Kamalvishnu Gottimukkala / Prashant Bajpai / Dinesh Ravindra Raju / Venkata Viswanadh Edara / Meredith E Davis-Gardner / Susanne Linderman / Kritika Dixit / Pragati Sharma / Grace Mantus / Narayanaiah Cheedarla / Hans P Verkerke / Filipp Frank / Andrew S Neish / John D Roback / Carl W Davis / Jens Wrammert / Rafi Ahmed / Mehul S Suthar / Amit Sharma / Kaja Murali-Krishna / Anmol Chandele / Eric A Ortlund / Abstract: Understanding the molecular features of neutralizing epitopes is important for developing vaccines/therapeutics against emerging SARS-CoV-2 variants. We describe three monoclonal antibodies (mAbs) ...Understanding the molecular features of neutralizing epitopes is important for developing vaccines/therapeutics against emerging SARS-CoV-2 variants. We describe three monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during the first wave of the pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, poorly neutralized Beta, and failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these mAbs in complex with trimeric spike protein showed that all three mAbs bivalently bind spike with two mAbs targeting class 1 and one targeting a class 4 receptor binding domain epitope. The immunogenetic makeup, structure, and function of these mAbs revealed specific molecular interactions associated with the potent multi-variant binding/neutralization efficacy. This knowledge shows how mutational combinations can affect the binding or neutralization of an antibody, which in turn relates to the efficacy of immune responses to emerging SARS-CoV-2 escape variants. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7uow.cif.gz | 723.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7uow.ent.gz | 592.3 KB | Display | PDB format |
PDBx/mmJSON format | 7uow.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7uow_validation.pdf.gz | 2.3 MB | Display | wwPDB validaton report |
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Full document | 7uow_full_validation.pdf.gz | 2.4 MB | Display | |
Data in XML | 7uow_validation.xml.gz | 129 KB | Display | |
Data in CIF | 7uow_validation.cif.gz | 192.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uo/7uow ftp://data.pdbj.org/pub/pdb/validation_reports/uo/7uow | HTTPS FTP |
-Related structure data
Related structure data | 26656MC 7u0qC 7u0xC M: map data used to model this data 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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-Components
#1: Protein | Mass: 133781.312 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus Gene: S, 2 / Cell line (production host): expi293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 48869.992 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi293 / Production host: Homo sapiens (human) #3: Antibody | Mass: 23225.838 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): expi293 / Production host: Homo sapiens (human) #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / Has ligand of interest | Y | |
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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
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Molecular weight | Experimental value: NO | |||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: C-flat-1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 297 K / Details: Wait time 20 seconds and blot time 3 seconds |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 81000 X / Nominal defocus max: 2600 nm / Nominal defocus min: 600 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 63.81 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 4186 |
EM imaging optics | Energyfilter slit width: 30 eV |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | |||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1604277 | |||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 146199 / Num. of class averages: 1 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||
Atomic model building | B value: 102 / Protocol: RIGID BODY FIT / Space: REAL / Target criteria: Correlation coefficient | |||||||||||||||||||||||||||||||||||
Refine LS restraints |
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