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- PDB-7mw5: Structure of the SARS-CoV-2 Spike trimer with one RBD down in com... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7mw5 | ||||||
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Title | Structure of the SARS-CoV-2 Spike trimer with one RBD down in complex with the Fab fragment of human neutralizing antibody clone 2 | ||||||
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![]() | VIRAL PROTEIN/Immune System / viral protein / antibody / VIRAL PROTEIN-Immune System complex | ||||||
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 / 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 / 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 | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.42 Å | ||||||
![]() | Hu, Y. / Xiong, Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617. Authors: Lei Peng / Yingxia Hu / Madeleine C Mankowski / Ping Ren / Rita E Chen / Jin Wei / Min Zhao / Tongqing Li / Therese Tripler / Lupeng Ye / Ryan D Chow / Zhenhao Fang / Chunxiang Wu / Matthew ...Authors: Lei Peng / Yingxia Hu / Madeleine C Mankowski / Ping Ren / Rita E Chen / Jin Wei / Min Zhao / Tongqing Li / Therese Tripler / Lupeng Ye / Ryan D Chow / Zhenhao Fang / Chunxiang Wu / Matthew B Dong / Matthew Cook / Guilin Wang / Paul Clark / Bryce Nelson / Daryl Klein / Richard Sutton / Michael S Diamond / Craig B Wilen / Yong Xiong / Sidi Chen / ![]() Abstract: COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging ...COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at ∼3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 766 KB | Display | ![]() |
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PDB format | ![]() | 624.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 24063MC ![]() 7mw2C ![]() 7mw3C ![]() 7mw4C ![]() 7mw6C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Antibody | Mass: 28634.998 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Antibody | Mass: 27758.316 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Protein | Mass: 142399.375 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 Production host: Mammalian expression vector pcDNA3.1-Flag (others) References: UniProt: P0DTC2 #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 |
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Sample preparation
Component | Name: the SARS-CoV-2 Spike trimer in complex with the Fab fragment of human neutralizing antibody clone 2 Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT | ||||||||||||
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Molecular weight | Value: 0.19 MDa / Experimental value: NO | ||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||
Specimen | Conc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 66.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.42 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 135336 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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