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Yorodumi- PDB-7chh: Cryo-EM structure of the SARS-CoV-2 S-6P in complex with BD-368-2 Fabs -
+Open data
-Basic information
Entry | Database: PDB / ID: 7chh | ||||||
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Title | Cryo-EM structure of the SARS-CoV-2 S-6P in complex with BD-368-2 Fabs | ||||||
Components |
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Keywords | ANTIVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 Spike / neutralizing antibody / ANTIVIRAL PROTEIN-IMMUNE SYSTEM 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 / 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 | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.49 Å | ||||||
Authors | Xiao, J. / Zhu, Q. / Wang, G. | ||||||
Citation | Journal: Cell / Year: 2020 Title: Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy. Authors: Shuo Du / Yunlong Cao / Qinyu Zhu / Pin Yu / Feifei Qi / Guopeng Wang / Xiaoxia Du / Linlin Bao / Wei Deng / Hua Zhu / Jiangning Liu / Jianhui Nie / Yinghui Zheng / Haoyu Liang / Ruixue Liu ...Authors: Shuo Du / Yunlong Cao / Qinyu Zhu / Pin Yu / Feifei Qi / Guopeng Wang / Xiaoxia Du / Linlin Bao / Wei Deng / Hua Zhu / Jiangning Liu / Jianhui Nie / Yinghui Zheng / Haoyu Liang / Ruixue Liu / Shuran Gong / Hua Xu / Ayijiang Yisimayi / Qi Lv / Bo Wang / Runsheng He / Yunlin Han / Wenjie Zhao / Yali Bai / Yajin Qu / Xiang Gao / Chenggong Ji / Qisheng Wang / Ning Gao / Weijin Huang / Youchun Wang / X Sunney Xie / Xiao-Dong Su / Junyu Xiao / Chuan Qin / Abstract: Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; ...Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" or "down" conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2's therapeutic potential in treating COVID-19. | ||||||
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 | 7chh.cif.gz | 652.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7chh.ent.gz | 542.8 KB | Display | PDB format |
PDBx/mmJSON format | 7chh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7chh_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7chh_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7chh_validation.xml.gz | 96.4 KB | Display | |
Data in CIF | 7chh_validation.cif.gz | 146.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ch/7chh ftp://data.pdbj.org/pub/pdb/validation_reports/ch/7chh | HTTPS FTP |
-Related structure data
Related structure data | 30374MC 7ch4C 7ch5C 7chbC 7chcC 7cheC 7chfC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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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 2 Gene: S, 2 / Cell (production host): 293F / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 24355.225 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): 293F / Production host: Homo sapiens (human) #3: Antibody | Mass: 23902.590 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): 293F / 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 | N | |
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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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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.2 | ||||||||||||||||||||||||
Specimen | Conc.: 0.02 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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 |
Image recording | Electron dose: 59.8 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 3.49 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 85053 / Symmetry type: POINT |