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Yorodumi- PDB-8swh: Local refinement of SARS-CoV-2 (HP-GSAS-Mut7) spike NTD in comple... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8swh | |||||||||
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Title | Local refinement of SARS-CoV-2 (HP-GSAS-Mut7) spike NTD in complex with TXG-0078 Fab | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / spike / COVID / monoclonal antibody / complex / NTD / VIRAL PROTEIN / VIRAL 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 / 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 2 Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.88 Å | |||||||||
Authors | Bangaru, B. / Ward, A. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell Rep / Year: 2024 Title: Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes. Authors: Jonathan Hurtado / Thomas F Rogers / David B Jaffe / Bruce A Adams / Sandhya Bangaru / Elijah Garcia / Tazio Capozzola / Terrence Messmer / Pragati Sharma / Ge Song / Nathan Beutler / ...Authors: Jonathan Hurtado / Thomas F Rogers / David B Jaffe / Bruce A Adams / Sandhya Bangaru / Elijah Garcia / Tazio Capozzola / Terrence Messmer / Pragati Sharma / Ge Song / Nathan Beutler / Wanting He / Katharina Dueker / Rami Musharrafieh / Sarah Burbach / Alina Truong / Michael J T Stubbington / Dennis R Burton / Raiees Andrabi / Andrew B Ward / Wyatt J McDonnell / Bryan Briney / Abstract: The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 ...The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8swh.cif.gz | 126 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8swh.ent.gz | 80.5 KB | Display | PDB format |
PDBx/mmJSON format | 8swh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8swh_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8swh_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8swh_validation.xml.gz | 39.2 KB | Display | |
Data in CIF | 8swh_validation.cif.gz | 54.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sw/8swh ftp://data.pdbj.org/pub/pdb/validation_reports/sw/8swh | HTTPS FTP |
-Related structure data
Related structure data | 40814MC 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: 141328.359 Da / Num. of mol.: 1 Mutation: R682G, R683S, R685S, V705C, F817P, T883C, A892P, A899P, A942P, K986P, V987P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 | ||
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#2: Antibody | Mass: 16115.957 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK Expi293 cells / Production host: Homo sapiens (human) | ||
#3: Antibody | Mass: 14484.454 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK Expi293 cells / Production host: Homo sapiens (human) | ||
#4: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-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 | Has ligand of interest | N | |
-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: Structure of SARS-CoV-2(HP-GSAS-Mut7) spike in complex with TXG-0078 Fab- Local refinement Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | |||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 | |||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Cell: 293F cells | |||||||||||||||
Buffer solution | pH: 7.4 / Details: 1X TBS | |||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: The spike protein was incubated with a 3-fold molar excess of TXG-0078 Fab for 30 minutes and mixed with 0.04 mM Lauryl maltose neopentyl glycol solution immediately prior to sample deposition. | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283 K |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 190000 X / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 4257 |
Image scans | Movie frames/image: 38 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.88 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 188799 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL Details: Initial fitting in chimera followed by relaxing in Coot | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7c2l Accession code: 7c2l / Source name: PDB / Type: experimental model |