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- PDB-7dk4: S-2H2-F3a structure, two RBDs are up and one RBD is down, each RB... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7dk4 | ||||||
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Title | S-2H2-F3a structure, two RBDs are up and one RBD is down, each RBD binds with a 2H2 Fab. | ||||||
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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 / ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Cong, Y. / Wang, Y.F. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections. Authors: Chao Zhang / Yifan Wang / Yuanfei Zhu / Caixuan Liu / Chenjian Gu / Shiqi Xu / Yalei Wang / Yu Zhou / Yanxing Wang / Wenyu Han / Xiaoyu Hong / Yong Yang / Xueyang Zhang / Tingfeng Wang / ...Authors: Chao Zhang / Yifan Wang / Yuanfei Zhu / Caixuan Liu / Chenjian Gu / Shiqi Xu / Yalei Wang / Yu Zhou / Yanxing Wang / Wenyu Han / Xiaoyu Hong / Yong Yang / Xueyang Zhang / Tingfeng Wang / Cong Xu / Qin Hong / Shutian Wang / Qiaoyu Zhao / Weihua Qiao / Jinkai Zang / Liangliang Kong / Fangfang Wang / Haikun Wang / Di Qu / Dimitri Lavillette / Hong Tang / Qiang Deng / Youhua Xie / Yao Cong / Zhong Huang / ![]() Abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for ...The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections. | ||||||
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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 | ![]() | 746.7 KB | Display | ![]() |
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PDB format | ![]() | 604.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 30702MC ![]() 7dccC ![]() 7dcxC ![]() 7dd2C ![]() 7dd8C ![]() 7dddC ![]() 7ddnC ![]() 7dk5C ![]() 7dk6C ![]() 7dk7C 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: 22822.611 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() #2: Antibody | Mass: 23975.307 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() #3: Protein | ![]() Mass: 140055.906 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: S, 2 / Cell line (production host): HEK293F / Production host: ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
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Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||
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![]() |
Image recording | Electron dose: 49.6 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction![]() | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 37641 / Symmetry type: POINT |