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- PDB-8dxu: Fab arms of antibodies GAR03 and 10G4 bound to the receptor bindi... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8dxu | ||||||
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Title | Fab arms of antibodies GAR03 and 10G4 bound to the receptor binding domain of SARS-CoV-2 in a 1:1:1 complex. | ||||||
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![]() | ANTIVIRAL PROTEIN / anti-CoV-2 / antibodies / convalescent patients / receptor binding domain. | ||||||
Function / homology | ![]() 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / 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 / 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 | ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() ![]() | ||||||
![]() | Langley, D.B. / Christ, D. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients. Authors: Romain Rouet / Jake Y Henry / Matt D Johansen / Meghna Sobti / Harikrishnan Balachandran / David B Langley / Gregory J Walker / Helen Lenthall / Jennifer Jackson / Stephanie Ubiparipovic / ...Authors: Romain Rouet / Jake Y Henry / Matt D Johansen / Meghna Sobti / Harikrishnan Balachandran / David B Langley / Gregory J Walker / Helen Lenthall / Jennifer Jackson / Stephanie Ubiparipovic / Ohan Mazigi / Peter Schofield / Deborah L Burnett / Simon H J Brown / Marianne Martinello / Bernard Hudson / Nicole Gilroy / Jeffrey J Post / Anthony Kelleher / Hans-Martin Jäck / Christopher C Goodnow / Stuart G Turville / William D Rawlinson / Rowena A Bull / Alastair G Stewart / Philip M Hansbro / Daniel Christ / ![]() ![]() Abstract: Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies ...Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 410.7 KB | Display | ![]() |
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PDB format | ![]() | 332.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 485.6 KB | Display | ![]() |
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Full document | ![]() | 494.5 KB | Display | |
Data in XML | ![]() | 37 KB | Display | |
Data in CIF | ![]() | 50.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7t5oC ![]() 7t72C ![]() 8dxtC C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
-Antibody , 4 types, 4 molecules HLAB
#2: Antibody | Mass: 24475.314 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Heavy chain of Fab arm of antibody 10G4 / Source: (gene. exp.) ![]() ![]() ![]() |
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#3: Antibody | Mass: 23591.232 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Light chain of Fab arm of antibody 10G4 / Source: (gene. exp.) ![]() ![]() ![]() |
#4: Antibody | Mass: 24705.656 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Heavy chain of Fab arm of antibody GAR03 / Source: (gene. exp.) ![]() ![]() ![]() |
#5: Antibody | Mass: 22970.273 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Light chain of Fab arm of antibody GAR03 / Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Sugars , 2 types, 2 molecules R![](data/chem/img/NAG.gif)
![](data/chem/img/NAG.gif)
#1: Protein | Mass: 22975.688 Da / Num. of mol.: 1 / Fragment: receptor binding domain Source method: isolated from a genetically manipulated source Details: SARS-CoV-2 receptor binding domain residues 333-528, with C-terminal 6His tag. Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Cell line (production host): ExpiCHO / Production host: ![]() ![]() |
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#6: Sugar | ChemComp-NAG / |
-Non-polymers , 2 types, 45 molecules ![](data/chem/img/CL.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/HOH.gif)
#7: Chemical | #8: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.4 Å3/Da / Density % sol: 44 % / Description: thin plates |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6 Details: Two uL of protein solution (~5 mg/mL of 1:1:1 complex in 25 mM Tris (pH 8.0), 200 mM NaCl) was combined with an equal volume of well solution (100 mM MMT buffer system (Molecular Dimensions) ...Details: Two uL of protein solution (~5 mg/mL of 1:1:1 complex in 25 mM Tris (pH 8.0), 200 mM NaCl) was combined with an equal volume of well solution (100 mM MMT buffer system (Molecular Dimensions) (pH 6.0), 19% (w/v) PEG6000. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 11, 2022 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9537 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.728→49.48 Å / Num. obs: 31192 / % possible obs: 99.4 % / Redundancy: 11.9 % / Biso Wilson estimate: 59.81 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.156 / Rpim(I) all: 0.047 / Rrim(I) all: 0.163 / Net I/σ(I): 12.8 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: ![]() | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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Processing
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Refinement | Method to determine structure: ![]() Starting model: generic fab and SARS-CoV-2 RBD Resolution: 2.728→45.547 Å / SU ML: 0.41 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 29.53 / 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: 164.75 Å2 / Biso mean: 64.0261 Å2 / Biso min: 27.48 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.728→45.547 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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Refinement TLS params. | Method: refined / Origin x: -9.5853 Å / Origin y: 11.3813 Å / Origin z: -58.3439 Å
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Refinement TLS group |
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