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Yorodumi- PDB-7y72: SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7y72 | |||||||||||||||||||||||||||
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Title | SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment of anti-RBD antibody E7 (focused refinement on Fab-RBD interface) | |||||||||||||||||||||||||||
Components |
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Keywords | VIRAL PROTEIN | |||||||||||||||||||||||||||
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 / 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 | Homo sapiens (human) | |||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.03 Å | |||||||||||||||||||||||||||
Authors | Chia, W.N. / Tan, C.W. / Tan, A.W.K. / Young, B. / Starr, T.N. / Lopez, E. / Fibriansah, G. / Barr, J. / Cheng, S. / Yeoh, A.Y.Y. ...Chia, W.N. / Tan, C.W. / Tan, A.W.K. / Young, B. / Starr, T.N. / Lopez, E. / Fibriansah, G. / Barr, J. / Cheng, S. / Yeoh, A.Y.Y. / Yap, W.C. / Lim, B.L. / Ng, T.S. / Sia, W.R. / Zhu, F. / Chen, S. / Zhang, J. / Greaney, A.J. / Chen, M. / Au, G.G. / Paradkar, P. / Peiris, M. / Chung, A.W. / Bloom, J.D. / Lye, D. / Lok, S.M. / Wang, L.F. | |||||||||||||||||||||||||||
Funding support | Singapore, Australia, United States, 8items
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Citation | Journal: Sci Adv / Year: 2023 Title: Potent pan huACE2-dependent sarbecovirus neutralizing monoclonal antibodies isolated from a BNT162b2-vaccinated SARS survivor. Authors: Wan Ni Chia / Chee Wah Tan / Aaron Wai Kit Tan / Barnaby Young / Tyler N Starr / Ester Lopez / Guntur Fibriansah / Jennifer Barr / Samuel Cheng / Aileen Ying-Yan Yeoh / Wee Chee Yap / Beng ...Authors: Wan Ni Chia / Chee Wah Tan / Aaron Wai Kit Tan / Barnaby Young / Tyler N Starr / Ester Lopez / Guntur Fibriansah / Jennifer Barr / Samuel Cheng / Aileen Ying-Yan Yeoh / Wee Chee Yap / Beng Lee Lim / Thiam-Seng Ng / Wan Rong Sia / Feng Zhu / Shiwei Chen / Jinyan Zhang / Madeline Sheng Si Kwek / Allison J Greaney / Mark Chen / Gough G Au / Prasad N Paradkar / Malik Peiris / Amy W Chung / Jesse D Bloom / David Lye / Sheemei Lok / Lin-Fa Wang / Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to ...The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo-electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure-dependent epitope. | |||||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7y72.cif.gz | 184.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7y72.ent.gz | 125.3 KB | Display | PDB format |
PDBx/mmJSON format | 7y72.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7y72_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7y72_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7y72_validation.xml.gz | 41.2 KB | Display | |
Data in CIF | 7y72_validation.cif.gz | 59.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y7/7y72 ftp://data.pdbj.org/pub/pdb/validation_reports/y7/7y72 | HTTPS FTP |
-Related structure data
Related structure data | 33651MC 7y71C 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: 132860.156 Da / Num. of mol.: 2 Mutation: R683A, R685A, F817P, A892P, A899P, A942P, K986P, V987P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: S, 2 / Cell line (production host): EXPI293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | | Mass: 23920.668 Da / Num. of mol.: 1 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: 23339.156 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): EXPI293 / Production host: Homo sapiens (human) |
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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
Component | Name: SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment of anti-RBD antibody E7 Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | |||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Cell: EXPI293 | |||||||||||||||
Buffer solution | pH: 7.4 | |||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment of anti-RBD antibody E7 | |||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
-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 / Nominal magnification: 81000 X / Nominal defocus max: 2400 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 4.76 sec. / Electron dose: 31.6 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 Details: Images were collected in counting mode at 25 frames per movie with an exposure time of 4.76 s per movie. |
EM imaging optics | Energyfilter slit width: 20 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: 402809 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.03 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 198525 / Details: Local refinement in cryoSPARC / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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Refine LS restraints |
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