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Yorodumi- PDB-8c89: SARS-CoV-2 spike in complex with the 17T2 neutralizing antibody F... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8c89 | |||||||||
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Title | SARS-CoV-2 spike in complex with the 17T2 neutralizing antibody Fab fragment (local refinement of RBD and Fab) | |||||||||
Components |
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Keywords | VIRAL PROTEIN / Complex SARS-CoV-2 Spike S 17T2 | |||||||||
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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / 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 | Severe acute respiratory syndrome coronavirus Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.41 Å | |||||||||
Authors | Modrego, A. / Carlero, D. / Bueno-Carrasco, M.T. / Santiago, C. / Carolis, C. / Arranz, R. / Blanco, J. / Magri, G. | |||||||||
Funding support | Spain, 2items
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Citation | Journal: Nat Commun / Year: 2024 Title: A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity. Authors: Leire de Campos-Mata / Benjamin Trinité / Andrea Modrego / Sonia Tejedor Vaquero / Edwards Pradenas / Anna Pons-Grífols / Natalia Rodrigo Melero / Diego Carlero / Silvia Marfil / César ...Authors: Leire de Campos-Mata / Benjamin Trinité / Andrea Modrego / Sonia Tejedor Vaquero / Edwards Pradenas / Anna Pons-Grífols / Natalia Rodrigo Melero / Diego Carlero / Silvia Marfil / César Santiago / Dàlia Raïch-Regué / María Teresa Bueno-Carrasco / Ferran Tarrés-Freixas / Ferran Abancó / Victor Urrea / Nuria Izquierdo-Useros / Eva Riveira-Muñoz / Ester Ballana / Mónica Pérez / Júlia Vergara-Alert / Joaquim Segalés / Carlo Carolis / Rocío Arranz / Julià Blanco / Giuliana Magri / Abstract: Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is ...Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in "up" position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8c89.cif.gz | 140.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8c89.ent.gz | 109.6 KB | Display | PDB format |
PDBx/mmJSON format | 8c89.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8c89_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 8c89_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8c89_validation.xml.gz | 46.8 KB | Display | |
Data in CIF | 8c89_validation.cif.gz | 66.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c8/8c89 ftp://data.pdbj.org/pub/pdb/validation_reports/c8/8c89 | HTTPS FTP |
-Related structure data
Related structure data | 16473MC 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: 23898.064 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus Gene: S, 2 / Cell (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 | ||
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#2: Antibody | Mass: 24231.311 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell (production host): Expi293 / Production host: Homo sapiens (human) | ||
#3: Antibody | Mass: 23686.299 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell (production host): Expi293 / Production host: Homo sapiens (human) | ||
#4: Polysaccharide | Source method: isolated from a genetically manipulated source Has ligand of interest | Y | |
-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: 7.6 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai F20 / Image courtesy: FEI Company |
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Microscopy | Model: TFS TALOS F200C |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 32 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 4.41 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 124570 / Symmetry type: POINT |